%PDF-1.3 % 1 0 obj << /Type/ExtGState /OPM 1 >> endobj 2 0 obj << /Type/ExtGState /FL 1 /SM 0.01 >> endobj 3 0 obj << /Type/ExtGState /OP true >> endobj 4 0 obj << /Type/ExtGState /OP false >> endobj 5 0 obj << /Length 10873 >> stream /GS0 gs /GS1 gs q /GS2 gs 0 0 0 0 k 307.559 51.023 242.362 631.654 re f 45.354 683.748 504.567 31.181 re f 45.354 99.024 242.363 413.7791 re f Q /GS2 gs q BT /F0 1 Tf 9.5 0 0 9.5 46.3543 439.9771 Tm 0 Tr 0 0 0 1 k 0.007 Tc 0 Tw (Summary. )Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 96.7807 439.9771 Tm 0 Tr 0 0 0 1 k 0.006 Tc 0.119 Tw (Apocrine carcinoma of the breast is a rare,)Tj -4.80251 -1.01619 TD 0.058 Tc 0.067 Tw (special type of breast carcinoma showing distinct)Tj T* 0.049 Tc 0.076 Tw (morphologic, immunohistochemical and molecular)Tj T* 0.075 Tc 0.483 Tw (genetic features. Apocrine epithelium has a)Tj T* 0.022 Tc 0.103 Tw (characteristic steroid receptor profile that is estrogen)Tj T* 0.074 Tc 0.051 Tw (receptor and progesterone receptor negative and)Tj T* 0.073 Tc 0.052 Tw (androgen receptor positive. This combination of)Tj T* 0 Tc 0.017 Tw (morphologic and immunohistochemical characteristics is)Tj T* 0.04 Tc 0.085 Tw (essential for the proper recognition of the apocrine)Tj T* 0.055 Tc 0.07 Tw (carcinomas. Strictly defined, apocrine carcinomas)Tj T* 0.021 Tc 0.104 Tw (express either Her)Tj 7.83753 0.00001 TD (-2/neu or EGFR, which along with)Tj -7.83753 -1.01619 TD 0.036 Tc 0.089 Tw (androgen receptor positivity make patients with the)Tj T* 0 Tc 0 Tw (apocrine carcinoma eligible for tar)Tj 13.80713 0 TD (geted therapies. )Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 9.5 0 0 9.5 46.3543 290.5971 Tm 0 Tr 0 0 0 1 k 0.043 Tc 0.096 Tw (Key words: )Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 106.4808 290.5971 Tm 0 Tr 0 0 0 1 k 0.038 Tc 0.087 Tw (Breast cancer)Tj 5.95898 0.00001 TD 0.0384 Tc (,)Tj 0.66332 0 Td 0.038 Tc (Special types, Apocrine)Tj -12.34864 -1.01619 TD 0 Tc 0 Tw (carcinoma, Androgen receptor )Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 9.5 0 0 9.5 46.3543 247.9171 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Introduction)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 63.3543 226.5771 Tm 0 Tr 0 0 0 1 k 0.075 Tc 0.067 Tw (Invasive carcinoma of the breast is the most)Tj -1.61905 -1.01619 TD 0.065 Tc 0.06 Tw [(common malignancy af)19(fecting women worldwide)]TJ T* 0.005 Tc 0.12 Tw ((Lakhani et al., 2012). It is a heterogeneous disease in)Tj T* 0 Tc 0.094 Tw [(morphologic, molecular and clinical terms \(W)82(eigelt and)]TJ T* 0.072 Tw [(Reis-Filho, 2009; W)80(eigelt et al., 2010a\). It encompasses)]TJ T* 0.103 Tw [(at least 20 dif)19(ferent morphologic variants among which)]TJ T* 0.01 Tc 0.114 Tw (invasive ductal carcinoma of no-special-type (NST) is)Tj T* 0.024 Tc 0.101 Tw (the most common type constituting up to 75% of all)Tj T* 0 Tc 0.065 Tw (breast carcinomas (Lakhani et al., 2012). The remaining)Tj T* 0.03 Tc 0.095 Tw (25% are so-called special histologic types including)Tj T* 0 Tc 0.124 Tw [(invasive apocrine carcinoma of the breast \(W)82(e)-1(i)-1(g)-1(e)-1(l)-1(t)-1( )-1(a)-1(n)-1(d)]TJ T* 0 Tw [(Reis-Filho, 2009; W)80(eigelt et al., 2010a\).)]TJ ET 0 0 0 0 k 307.559 51.023 242.362 461.221 re f Q /GS3 gs /GS2 gs q BT /F0 1 Tf 9.5 0 0 9.5 308.559 439.9771 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Definition)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 325.559 418.6371 Tm 0 Tr 0 0 0 1 k 0 Tc 0.028 Tw (Mammary apocrine cells have abundant eosinophilic)Tj -1.61905 -1.01619 TD 0.023 Tc 0.102 Tw (and granular cytoplasm (\322type A\323 cells), centrally to)Tj T* 0 Tc 0.067 Tw (eccentrically located nuclei with prominent nucleoli and)Tj T* 0.008 Tc 0.117 Tw [(distinctive cell borders \(Eusebi et al., 1986; T)72(avassoli,)]TJ T* 0.016 Tc 0.109 Tw (1999; Jones et al., 2001; Page, 2005\) \(Figs. 1A, 2A\).)Tj T* 0.031 Tc 0.094 Tw [(A)1(n)1(o)1(t)1(h)1(e)1(r)41(, less common type of apocrine cells, called)]TJ T* 0.008 Tc 0.117 Tw (\322type B\323 cells (Lakhani et al., 2012), has more foamy)Tj T* 0.075 Tc 0.229 Tw (and vacuolated cytoplasm (Fig. 1B). Apocrine)Tj T* 0.002 Tc 0 Tw (dif)Tj 1.09988 0.00001 TD 0.123 Tw (ferentiation (metaplasia) is commonly seen in breast)Tj -1.09988 -1.01619 TD 0.004 Tc 0.121 Tw (tissue, particularly in the context of fibrocystic disease)Tj T* (of the breast, although it may be associated with other)Tj T* 0 Tc 0.096 Tw (benign and malignant conditions \(Durham and Fechner)Tj 22.64164 0 TD (,)Tj -22.64164 -1.01619 TD 0.03 Tc 0.095 Tw (2000; O\325Malley and Bane, 2004, 2008; Masood and)Tj T* 0.018 Tc 0.107 Tw (Rosa, 2009\). The benign breast lesions with apocrine)Tj T* 0.075 Tc 0.055 Tw (morphology include papillary apocrine changes,)Tj T* 0.013 Tc 0.112 Tw (apocrine cysts, apocrine adenosis \(sclerosing adenosis)Tj T* 0.06 Tc 0.065 Tw (with apocrine metaplasia\), and apocrine adenoma)Tj T* (\(Durham and Fechner)Tj 10.00272 0.00001 TD 0.0599 Tc (,)Tj 0.68487 0 Td 0.06 Tc (2000\). Malignant apocrine)Tj -10.68759 -1.01621 TD 0.001 Tc 0.124 Tw (lesions of the breast include apocrine ductal carcinoma)Tj 0 -1.01619 TD 0.075 Tc 0.078 Tw (in situ (DCIS) and invasive apocrine carcinoma)Tj T* 0 Tc 0 Tw ((Gerhard et al., 2012). )Tj 1.61905 -1.01619 TD 0.016 Tc 0.109 Tw (The presence of malignant apocrine cells in more)Tj -1.61905 -1.01619 TD 0.043 Tc 0.082 Tw (than 90% of the tumor population defines invasive)Tj T* 0 Tc 0.065 Tw [(apocrine carcinoma \(O\325Malley et al., 201)39(1\). The lack of)]TJ T* 0.042 Tw (uniform acceptance/application of diagnostic criteria has)Tj T* 0.122 Tw (resulted in various and frequently confusing definitions)Tj T* 0.001 Tc 0.124 Tw (and thresholds for definitions of apocrine carcinoma in)Tj T* 0 Tc 0.092 Tw (the available literature \(Bundred et al., 1990; Matsuo et)Tj T* 0.011 Tc 0.114 Tw (al., 1998; Japaze et al., 2005; Rosen and Hoda, 2006;)Tj T* 0.026 Tc 0.099 Tw [(T)70(anaka et al., 2008; Iwase et al., 2010; Lewis et al.,)]TJ T* 0 Tc 0 Tw (201)Tj 1.46314 0.00001 TD 0.087 Tw (1; Lakhani et al., 2012; Cha et al., 2012; Dag et al.,)Tj -1.46314 -1.01619 TD 0.074 Tw [(2012; T)70(sutsumi, 2012; Choi et al., 2012\). Moreover)40(, the)]TJ T* 0.112 Tw (most recent WHO classification of breast tumors of)Tj 21.39336 0.00001 TD 0 Tw (fers)Tj -21.39336 -1.0162 TD 0.024 Tc 0.101 Tw (an imprecise definition of apocrine carcinoma of the)Tj 0 -1.01619 TD 0 Tc 0 Tw (breast (Lakhani et al., 2012). )Tj ET 0 0 0 0 k 45.354 675.213 504.567 38.031 re f 45.354 448.157 504.567 226.772 re f Q /GS3 gs /GS2 gs q BT /F2 1 Tf 18.5 0 3.9323 18.5 265.7686 660.4469 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Review)Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 18.5 0 0 18.5 46.3543 615.0929 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Apocrine carcinoma of the breast: )Tj 0 -1.22579 TD -0.0002 Tc (A)Tj 0.99966 0 Td 0 Tc (comprehensive review)Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 9.5 0 0 9.5 46.3543 568.6853 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Semir Vranic)Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 7.125 0 0 7.125 104.4259 571.8204 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (1,2)Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 9.5 0 0 9.5 114.3271 568.6853 Tm 0 Tr 0 0 0 1 k -0.0001 Tc (,)Tj 0.55576 0 Td 0 Tc 0 Tw (Fernando Schmitt)Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 7.125 0 0 7.125 200.3443 571.8204 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (3,4)Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 9.5 0 0 9.5 210.2456 568.6853 Tm 0 Tr 0 0 0 1 k -0.0001 Tc (,)Tj 0.55584 0 Td 0 Tc 0 Tw (Anna Sapino)Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 7.125 0 0 7.125 273.575 571.8204 Tm 0 Tr 0 0 0 1 k 0 Tc (2)Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 9.5 0 0 9.5 277.5359 568.6853 Tm 0 Tr 0 0 0 1 k 0 Tc (,)Tj -24.3349 -1.34273 TD 0 Tw (Jose Luis Costa)Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 7.125 0 0 7.125 119.1907 559.0645 Tm 0 Tr 0 0 0 1 k 0 Tc (4)Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 9.5 0 0 9.5 123.1516 555.9293 Tm 0 Tr 0 0 0 1 k -0.0001 Tc (,)Tj 0.55575 0 Td 0 Tc 0 Tw (Sandeep Reddy)Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 7.125 0 0 7.125 199.685 559.0645 Tm 0 Tr 0 0 0 1 k 0 Tc (5)Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 9.5 0 0 9.5 203.6459 555.9293 Tm 0 Tr 0 0 0 1 k -0.0002 Tc (,)Tj 0.55567 0 Td 0 Tc 0 Tw (Michael Castro)Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 7.125 0 0 7.125 276.48 559.0645 Tm 0 Tr 0 0 0 1 k 0 Tc (5)Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 9.5 0 0 9.5 283.0802 555.9293 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (and Zoran Gatalica)Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 7.125 0 0 7.125 368.5849 559.0645 Tm 0 Tr 0 0 0 1 k 0 Tc (5)Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 6.375 0 0 6.375 46.3543 545.9784 Tm 0 Tr 0 0 0 1 k 0 Tc (1)Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 8.5 0 0 8.5 49.8982 543.1733 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Department of Pathology, Clinical Center of the University of Sarajevo, Sarajevo, Bosnia and Herzegovina, )Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 6.375 0 0 6.375 452.7787 545.9784 Tm 0 Tr 0 0 0 1 k 0 Tc (2)Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 8.5 0 0 8.5 456.3226 543.1733 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Department of Medical)Tj -48.23156 -1.50072 TD (Sciences, University of Turin, Turin, Italy, )Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 6.375 0 0 6.375 203.1374 533.2224 Tm 0 Tr 0 0 0 1 k 0 Tc (3)Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 8.5 0 0 8.5 206.6813 530.4173 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Department of Pathology and Oncology, Medical Faculty of Porto University, Porto,)Tj -18.862 -1.50071 TD (Portugal, )Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 6.375 0 0 6.375 85.0858 520.4664 Tm 0 Tr 0 0 0 1 k 0 Tc (4)Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 8.5 0 0 8.5 88.6297 517.6613 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal and )Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 6.375 0 0 6.375 448.068 520.4664 Tm 0 Tr 0 0 0 1 k 0 Tc (5)Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 8.5 0 0 8.5 451.6119 517.6613 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Caris Life Sciences,)Tj -47.67736 -1.5007 TD (Phoenix, Arizona, United States of America)Tj ET 0 0 0 0 k 45.354 731.244 394.761 12 re f BT /F3 1 Tf 8.5 0 0 8.5 46.3543 736.0495 Tm 0 0 0 1 k (Histol Histopathol (2013) 28: 1393-1409)Tj ET 0 0 0 0 k 45.354 51.023 242.363 21.837 re f Q /GS3 gs /GS2 gs q BT /F4 1 Tf 7.5 0 1.59418 7.5 46.3543 66.3945 Tm 0 Tr 0 0 0 1 k 0.033 Tc 0.106 Tw (Offprint requests to: )Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 122.1529 66.3945 Tm 0 Tr 0 0 0 1 k 0.033 Tc 0.106 Tw (Zoran Gatalica, MD, DSc, 4610 S 44th Place)Tj -10.1065 -1.4227 TD 0 Tc 0 Tw (Phoenix, AZ 85040, USA. e-mail: zgatalica@carisls.com)Tj ET 0 J 0 j 10 M []0 d 0.567 w 0 0 0 1 K 45.354 74.846 m 287.717 74.846 l S 45.354 272.5721 m 287.717 272.5721 l S 0 0 0 0 k 45.354 709.929 242.363 21 re f Q /GS3 gs /GS2 gs q BT /F0 1 Tf 9.5 0 0 9.5 46.3543 713.0095 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (http://www.hh.um.es)Tj ET 0 0 0 0 k 441.449 709.898 108.472 33.346 re f Q /GS3 gs /GS2 gs q BT /F0 1 Tf 14.5 0 0 14.5 442.4488 731.6769 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Histology and)Tj 0 -1.2 TD (Histopathology)Tj ET 0 0 0 0 k 438.395 692.22 111.526 15.104 re f Q /GS3 gs /GS2 gs q BT /F4 1 Tf 7 0 1.4879 7 446.9046 701.2222 Tm 0 Tr 0 0 0 1 k -0.0002 Tc (C)Tj 0.72178 0.00001 TD 0 Tc 0 Tw (ellular and Molecular Biology)Tj ET Q endstream endobj 6 0 obj << /Width 920 /ColorSpace/DeviceCMYK /Filter/DCTDecode /Subtype/Image /Height 381 /Type/XObject /Length 421864 /BitsPerComponent 8 >> stream JFIFAdobeeC     C  } }!1AQa"q2#BR$3br %&'()*456789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz w!1AQaq"2B #3Rbr $4%&'()*56789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz?QjO۶/c_W!{ӢĦ'|e J8?C \oq!_3 ~ڎFpIkLGʞ~)FXaN6'ޓ-1^יּcѻEKx~Uw90?BX5Ug'i'u_'䊠?I*fڪ.rys^O-:>$e/bSsSG_08X!?,UHN$m I^ @+x EThM\;AO'`ü?Wj/"w '2yq2kb:}{W5oO SFVQm/ߕ6{AO'`ü?Wj/" jY?&j^u_'} Ggu.ɳ(~:9潚@O0_ejh] `q?BX5Wg`;ץEO6k{$dBveOY@8g6YB0rq-EN1/(.5} `q?BX5X7Eڧf]{?*@Oq)vq?>u_'}_ +cY BN*$\"~&%9CrycniG/4,|Wa'Q|Og& (:nIӏqeB?|=*_XStܣt"nKU_f/`x b_EGkJ[qُ__q^~Ũė޹.&?"a'Q|O'k *?ฬ_?t~̚^xcJ?پZ~%s6r\L~.)?v7{iDO:x b_E+6FI*HC ˯`ӟSDxd͉WեށSG_08X!?,UHas#&s\ܣS1xc&+u<$_66!/AO'`ü?Wj/"[2?Vu?-fMGZ"}8Mӎk)Jw^M*MBJ ;1OxL_x/Hq?BX5KqQY c|27ծlzЇ)fT=Os+ӌ1poVj2DzSpܭt?`ü?Wj/"o&Qy?\Ƚ5>k_ПdR_MX$G)rWXw*E?$RMK["I7'f׶_W^ ~'9dX7ib#~KrC W,{UPx b_E5p5[% 8cb.xYЏDO:x b_EAkCm2Iuws[NȚz}n-vDO;x b_EL?_IS#D\c_ٛ^ھ?h޹~? 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This reported tenfold variation is probably due)Tj T* 0.011 Tw (to the lack of consistent and accepted criteria \(Mossler et)Tj T* 0.051 Tc 0.074 Tw (al., 1980; Eusebi et al., 1986; Pagani et al., 1994;)Tj T* 0.008 Tc 0.117 Tw [(T)70(akeuchi et al., 2004; Japaze et al., 2005; Celis et al.,)]TJ 0 -1.01618 TD 0 Tc 0.116 Tw [(2006; Rosen and Hoda 2006; W)80(ells and El-A)92(yat, 2007;)]TJ 0 -1.01619 TD 0.019 Tc 0.106 Tw [(Kreike et al., 2007; W)81(eigelt et al., 2008; Kaya et al.,)]TJ T* 0 Tc 0.026 Tw [(2008; T)70(anaka et al., 2008; Bhar)19(gava et al., 2009; Neimer)]TJ T* 0.024 Tw [(et al., 2010; Iwase et al., 2010; Lewis et al., 201)39(1; T)70(an et)]TJ T* 0.079 Tw (al., 201)Tj 3.01407 0 TD (1; Choi et al., 2012; Monhollen et al., 2012, Lin)Tj -3.01407 -1.01619 TD 0.069 Tw (Fde et al., 2012; Choi et al., 2012; Lakhani et al., 2012;)Tj T* 0 Tw (Dellapasqua et al., 2013\). )Tj 1.61905 -1.01619 TD 0.075 Tc 0.157 Tw (Rare cases of in situ and invasive apocrine)Tj -1.61905 -1.01619 TD 0 Tc 0.085 Tw (carcinomas among men have also been described \(Shah)Tj T* 0.098 Tw (et al., 1980; Bryant, 1981; Arnould et al., 2006; Dag et)Tj T* 0 Tw (al., 2012\).)Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 9.5 0 0 9.5 46.3543 360.6465 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Histologic and ultrastructural characteristics)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 63.3543 339.3065 Tm 0 Tr 0 0 0 1 k 0.061 Tc 0.064 Tw (Apocrine carcinomas typically exhibit growth)Tj -1.61905 -1.01619 TD 0.028 Tc 0.097 Tw (patterns similar to invasive ductal carcinomas, NST)Tj 22.64166 0 TD 0 Tc (,)Tj -22.64166 -1.01619 TD 0.057 Tc 0.068 Tw (including a rare encysted (encapsulated) apocrine)Tj T* 0.009 Tc 0.116 Tw (papillary carcinoma of the breast that usually presents)Tj ET 0 0 0 0 k 307.559 300.124 242.362 388.803 re f BT /F1 1 Tf 10.5 0 0 10.5 308.559 680.7465 Tm 0 0 0 1 k 0 Tc 0.036 Tw (grossly as a cyst and is microscopically well demarcated)Tj 0 -1.01619 TD 0 Tw [(\(Seal et al., 2009; Lafor)19(ga et al., 201)37(1\).)]TJ 1.61905 -1.01619 TD 0.067 Tc 0.058 Tw (Apocrine carcinomas are graded according to)Tj -1.61905 -1.01618 TD 0.001 Tc 0.124 Tw (Elston-Ellis modification of the Bloom and Richardson)Tj 0 -1.01619 TD 0 Tc 0.036 Tw (grading system (Elston and Ellis, 1991). The majority of)Tj T* 0.015 Tc 0.11 Tw (apocrine carcinomas are grade 2 and 3 \(Eusebi et al.,)Tj T* 0 Tc 0.064 Tw [(1986; T)70(anaka et al., 2008; V)61(ranic et al., 2010; Bhar)18(gava)]TJ T* 0.027 Tw [(et al., 2010; T)71(sutsumi, 2012; Cha et al., 2012; Alvarenga)]TJ T* 0.123 Tw (et al., 2012\). Mitotic activity in apocrine carcinomas is)Tj T* 0.121 Tw (usually moderate to high, particularly in triple negative)Tj 0 -1.01618 TD 0.067 Tw [(apocrine carcinomas \(Choi et al., 2012; T)72(sutsumi, 2012;)]TJ 0 -1.01619 TD 0 Tw (Alvarenga et al., 2012\).)Tj 1.61905 -1.01619 TD 0.012 Tc 0.113 Tw (Like the more common invasive ductal carcinoma)Tj -1.61905 -1.01619 TD 0.02 Tc 0.105 Tw [(NST)73(, invasive apocrine carcinoma may be associated)]TJ T* 0.019 Tc 0.106 Tw (with an in situ apocrine component (apocrine DCIS).)Tj T* 0.025 Tc 0.1 Tw (The relationship of apocrine carcinoma of the breast)Tj T* 0 Tc 0.001 Tw (with other benign apocrine lesions is not well established)Tj T* 0.059 Tc 0.066 Tw (although some of them \(e.g. apocrine metaplasia/)Tj 0 -1.01618 TD 0.05 Tc 0.075 Tw (hyperplasia, apocrine adenosis\) may harbor clonal)Tj 0 -1.01619 TD 0.008 Tc 0.117 Tw (origins and premalignant potential \(Selim et al., 2000;)Tj T* 0 Tc 0 Tw (Schmitt and Reis-Filho, 2002\).)Tj 1.61905 -1.01619 TD 0.075 Tc 0.154 Tw [(Ultrastructurally)66(, apocrine cells have a rich)]TJ -1.61905 -1.01619 TD 0.008 Tc 0.117 Tw (cytoplasm with well-defined outlines. Their cytoplasm)Tj T* 0.044 Tc 0.081 Tw (contains electron-dense membrane granules, empty)Tj T* 0.075 Tc 0.257 Tw (vesicles, prominent Golgi apparatus and lar)Tj 21.87283 0 TD 0 Tw (ge)Tj -21.87283 -1.01619 TD 0.021 Tc 0.104 Tw (mitochondria with incomplete cristae \(Mossler et al.,)Tj T* 0 Tc 0.111 Tw [(1980; Roddy and Silverber)18(g, 1980; Eusebi et al., 1986;)]TJ T* 0.125 Tw (Alexiev et al., 1994\). Like normal apocrine glands, the)Tj T* 0.075 Tc 0.087 Tw (cytoplasm of the apocrine tumor cells may also)Tj T* 0.066 Tc 0.059 Tw (accumulate lipids but the extent of accumulation)Tj T* 0.012 Tc 0.113 Tw ((measured by the specific lipid marker adipophilin) is)Tj T* 0.018 Tc 0.107 Tw (never as prominent as in lipid-rich breast carcinomas)Tj T* 0 Tc 0.052 Tw (\(Moritani et al., 201)Tj 8.14395 0 TD (1\). The nuclei tend to be round with)Tj -8.14395 -1.01619 TD 0.008 Tc 0.117 Tw (condensed chromatin and lar)Tj 12.06209 0 TD (ge nucleoli \(Eusebi et al.,)Tj -12.06209 -1.01619 TD 0.039 Tc 0.086 Tw (1986\). Grekou et al. also described the presence of)Tj T* 0.026 Tc 0.099 Tw (intranuclear helioid inclusions in the apocrine tumor)Tj ET 0 0 0 0 k 45.354 729.071 504.567 14.1729 re f Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.7 0 0 7.7 46.3543 731.757 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (1394)Tj ET 0 0 0 0 k 45.354 715.927 504.567 12.002 re f 45.354 689.417 504.567 25.512 re f 45.354 715.927 504.567 12.002 re f Q /GS3 gs /GS2 gs q BT /F4 1 Tf 10.5 0 2.23185 10.5 220.6233 719.277 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Apocrine carcinoma of the breast)Tj ET 0 0 0 0 k 45.354 63.62 504.567 207.972 re f /GS3 gs q 45.354 63.62 504.567 207.972 re W n /Fm0 Do Q /GS2 gs 45.354 40.252 504.567 19.336 re f Q /GS3 gs /GS2 gs q BT /F0 1 Tf 7.5 0 0 7.5 46.3543 53.1222 Tm 0 Tr 0 0 0 1 k 0 Tc 0.005 Tw (Fig. 1. )Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 70.1783 53.1222 Tm 0 Tr 0 0 0 1 k 0 Tc 0.005 Tw (Two different apocrine carcinoma cases. )Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 7.5 0 0 7.5 207.0462 53.1222 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (A.)Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 216.6647 53.1222 Tm 0 Tr 0 0 0 1 k -0.0002 Tc (A)Tj 0.94956 0 Td 0 Tc 0.005 Tw (case composed predominantly of the )Tj ET Q /GS3 gs /GS2 gs q BT /F4 1 Tf 7.5 0 1.59418 7.5 348.5852 53.1222 Tm 0 Tr 0 0 0 1 k 0 Tc 0.005 Tw (Type A cells)Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 391.6169 53.1222 Tm 0 Tr 0 0 0 1 k 0 Tc 0.005 Tw (with abundant eosinophilic cytoplasm and large)Tj -46.035 -1.2 TD 0 Tw (nuclei with prominent nucleoli. )Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 7.5 0 0 7.5 148.4484 44.1222 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (B.)Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 158.0303 44.1222 Tm 0 Tr 0 0 0 1 k -0.0001 Tc (A)Tj 0.94472 0 Td 0 Tc 0 Tw (case composed of the )Tj ET Q /GS3 gs /GS2 gs q BT /F4 1 Tf 7.5 0 1.59418 7.5 240.5578 44.1222 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Type B cells)Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 283.4796 44.1222 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (with foamy cytoplasm. 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[>ʫ QHr)zI7ӢScf?5øg+m?_ [WL?Aӯի#P arJ|g\ܼ` _I}"< ImXzl=}(|4i&fsOkc}DV]sW?%u;Z y*K&f|eL(q^61N}׍?fc_ t/i~ XשAgjU$W҄nzo/syi'_ЭdٴXV/j~4"thZ cqu4+Y-n=q;U c.:IA{Z6o۾ϧjN|EZpqtC(usg_? 5ѧ<<ھ WVs3o?:fK_,c8k?[j-z*ZM[x}+O&t`/)Kڲsp[শaWmw?R8FPk/*gdN|sm -xoMWIG[lNU9ʁp6W|DJ?)0>뤯ך.*@x=ĵSNPi޳"~}J8SeFܿV/x~kZ_ZxP7mWY6S|}{RD v WE]MkiKǟSk?~o/]KeY?ੲ+ dŒ?ư^C9Z3KX:<_TgeQkk|l/vZO7"5cN.jIm>Um=/%jQ'x?1myҟkzrn~S#،\8B՜/>fR!TVF19OqiFҥcx㏃K2qm޳| C,X`q^:-w~Ksi? 񾠣@z?J0slV,+ڶxn7|xV/|EQY0,PXd@uk[V;4Hx4mi> kYzׯ>SZ4kE7潞~ELƅ7Z jhT3b> (gDaG*#Ujt)Mgr9qpꔥƍm>^1?K?o֖bz?Γ|;s%s6F%v ?:[1A/0$qe.kne_#L/|55c]F C/%/O)5}!K[\ }o70}^OӬob=u!Ӓѵ3eU/[BȸKE_X.(Sŕ_vJT8:ӫ'kO\x)Ш-9[nܿV=C[κ$lz7kX`v498xZJwO7E.v'~\_gK3,Tka1)JR7 EZs;y'~1]cZW|In$t<[1T_že!5O¬us8ufH~iL'[1eVw߳G3w^+QԼy~FLC?@\ '׭oZ+"yk Bg}Zϵ'9Nwv~VmtնZ%Xzגx?HĖ_STO*o_aZyw{}ZQc>/ProcSet[/PDF/ImageC]/ExtGState<>>> /Type/XObject /Length 35 /Matrix[1 0 0 1 0 0] /OPI<> >> /FormType 1 >> stream /GS1 gs q 1 0 0 1 0 0 cm /Im2 Do Q endstream endobj 12 0 obj << /Name/Fm2 /BBox[0 0 595.27594 782.92896] /Subtype/Form /Resources<>/ProcSet[/PDF]/ExtGState<>>> /Type/XObject /Length 59 /Matrix[1 0 0 1 0 0] /OPI<> >> /FormType 1 >> stream /GS1 gs q 504.56241 0 0 393.366 44.521 63.496 cm /Fm3 Do Q endstream endobj 13 0 obj << /Length 5276 >> stream /GS0 gs /GS1 gs q /GS2 gs 0 0 0 0 k 45.354 483.525 242.363 205.402 re f Q /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 46.3543 680.7465 Tm 0 Tr 0 0 0 1 k 0.043 Tc 0.082 Tw (cells. These inclusions represent single membrane-)Tj 0 -1.01619 TD 0.007 Tc 0.118 Tw (bounded bodies that have also been described in other)Tj T* 0.042 Tc 0.082 Tw (benign breast lesions (e.g. benign hyperplasia) and)Tj 0 -1.01618 TD 0 Tc 0.109 Tw (extramammary malignancies \(e.g. acinic cell carcinoma)Tj 0 -1.01619 TD 0 Tw (of the salivary gland\) \(Grekou et al., 1999\).)Tj 1.61905 -1.01619 TD 0.111 Tw [(Apocrine dif)18(ferentiation can be seen in other breast)]TJ -1.61905 -1.01619 TD 0.003 Tc 0.122 Tw [(carcinoma subtypes including papillary)67(, micropapillary)66(,)]TJ T* 0 Tc 0.06 Tw [(tubular)40(, medullary)66(, and lobular carcinoma \(Eusebi et al.,)]TJ T* 0.049 Tc 0.076 Tw [(1984, 1992; Page, 2005; W)80(ells and El-A)92(yat, 2007;)]TJ T* 0.075 Tc 0.188 Tw (Lakhani et al., 2012\). Of particular interest is)Tj T* 0.065 Tw (pleomorphic lobular carcinoma, a rare but more)Tj T* 0 Tc 0.045 Tw (aggressive variant of lobular carcinoma that may exhibit)Tj 0 -1.01618 TD 0.014 Tc 0.111 Tw (morphologic similarities with apocrine carcinoma and)Tj 0 -1.01619 TD 0.001 Tc 0.124 Tw (frequently clusters with it creating \322molecular apocrine)Tj 0 -1.01618 TD 0.041 Tc 0.084 Tw [(tumors\323 \(Eusebi et al., 1992; W)81(eigelt et al., 2008\).)]TJ 0 -1.01619 TD 0.006 Tc 0.119 Tw (Pleomorphic lobular carcinomas also show GCDFP-15)Tj T* 0.014 Tc 0.111 Tw [(positivity)65(, but typically have discohesive pleomorphic)]TJ T* 0.031 Tc 0.093 Tw (tumor cells that lose E-cadherin expression as other)Tj 0 -1.01618 TD 0 Tc 0.053 Tw (lobular carcinoma variants \(Eusebi et al., 1992; Palacios)Tj ET 0 0 0 0 k 307.559 482.457 242.362 206.929 re f BT /F1 1 Tf 10.5 0 0 10.5 308.559 681.2054 Tm 0 0 0 1 k 0.001 Tw (et al., 2003; Reis-Filho et al., 2005; Simpson et al., 2008;)Tj 0 -1.01619 TD 0.021 Tc 0.104 Tw [(W)80(eigelt et al., 2008, 2010b; Monhollen et al., 2012\).)]TJ T* 0 Tc 0.125 Tw (Pleomorphic lobular carcinomas tend to be ER and PR)Tj T* 0.014 Tc 0.111 Tw (positive (~80%) but may also be positive for AR and)Tj T* 0 Tc 0.087 Tw [(Her)19(-2/neu protein \(Middleton et al., 2000; Reis-Filho et)]TJ T* 0.048 Tw (al., 2005; Simpson et al., 2008; Chen et al., 2009\). They)Tj T* 0.005 Tc 0.12 Tw (may also show foci of classical lobular carcinoma and)Tj T* 0.024 Tc 0.101 Tw (are frequently associated with LCIS \(or pleomorphic)Tj T* 0 Tc 0.041 Tw (LCIS\) \(Eusebi et al., 1992; Middleton et al., 2000; Reis-)Tj T* 0.047 Tc 0.078 Tw (Filho et al., 2005\). In contrast, in typical apocrine)Tj T* 0.008 Tc 0.117 Tw (carcinomas, cells do not tend to show discohesiveness)Tj T* 0.005 Tc 0.12 Tw [(and retain E-cadherin expression \(W)81(eigelt et al., 2008;)]TJ 0 -1.01618 TD 0.006 Tc 0.119 Tw (Paredes et al., 2008; Choi et al., 2012\). A histiocytoid)Tj 0 -1.01619 TD 0.034 Tc 0.091 Tw [(variant of lobular carcinomas is another dif)20(ferential)]TJ T* 0 Tc 0.101 Tw (diagnosis because a subset of apocrine carcinomas may)Tj 0 -1.01618 TD 0.004 Tc 0.121 Tw (have the tumor cells with foamy vacuolated cytoplasm)Tj 0 -1.01619 TD 0.012 Tc 0.113 Tw (\(\322type B\323 cells\) \(Damiani et al., 1998; Lakhani et al.,)Tj T* 0 Tc 0.025 Tw (2012\). Histiocytoid lobular cells however tend to show a)Tj 0 -1.01618 TD 0.015 Tc 0.11 Tw [(bland cytomorphology)65(, loss of E-cadherin expression,)]TJ ET 0 0 0 0 k 45.354 729.071 504.567 14.1729 re f Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.7 0 0 7.7 531.7993 731.757 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (1395)Tj ET 0 0 0 0 k 45.354 716.262 504.567 12 re f 45.354 689.417 504.567 25.512 re f 45.354 716.262 504.567 12 re f Q /GS3 gs /GS2 gs q BT /F4 1 Tf 10.5 0 2.23185 10.5 220.6233 719.6104 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Apocrine carcinoma of the breast)Tj ET 0 0 0 0 k 45.354 63.4961 504.567 392.533 re f /GS3 gs q 45.354 63.4961 504.567 392.533 re W n /Fm2 Do Q /GS2 gs 45.354 40.252 504.567 19.382 re f Q /GS3 gs /GS2 gs q BT /F0 1 Tf 7.5 0 0 7.5 46.3543 53.1687 Tm 0 Tr 0 0 0 1 k 0 Tc 0.1 Tw (Fig. 2. A. )Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 81.9299 53.1687 Tm 0 Tr 0 0 0 1 k -0.0002 Tc (A)Tj 1.0444 0 Td 0 Tc 0.1 Tw (case of invasive apocrine carcinoma with characteristic morphology. )Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 7.5 0 0 7.5 323.686 53.1687 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (B-C.)Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 341.9258 53.1687 Tm 0 Tr 0 0 0 1 k 0 Tc 0.1 Tw (Steroid receptor profile: Estrogen receptor (ER)-negative )Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 7.5 0 0 7.5 536.4315 53.1687 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw ((B))Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 546.8374 53.1687 Tm 0 Tr 0 0 0 1 k 0 Tc (;)Tj -66.7311 -1.2 TD 0 Tw (Androgen receptor (AR)-positive )Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 7.5 0 0 7.5 155.9466 44.1687 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw ((C))Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 166.3525 44.1687 Tm 0 Tr 0 0 0 1 k 0 Tc (.)Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 7.5 0 0 7.5 170.52 44.1687 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (D.)Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 180.1019 44.1687 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (The tumor cells also exhibited Her-2/neu protein overexpression (score 3+).)Tj ET Q endstream endobj 14 0 obj << /Length 11885 >> stream /GS0 gs /GS1 gs q /GS2 gs 0 0 0 0 k 45.354 44.149 242.363 645.2371 re f Q /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 46.3543 681.2054 Tm 0 Tr 0 0 0 1 k 0.015 Tc 0.11 Tw [(and exhibit strikingly dif)19(ferent ultrastructural features)]TJ 0 -1.01619 TD 0.046 Tc 0.079 Tw [(\(Gupta et al., 2002; T)71(an et al., 201)37(1\). Histiocytoid)]TJ T* 0 Tc 0.014 Tw (carcinomas are also associated with lobular carcinoma in)Tj T* 0.014 Tc 0.111 Tw (situ (LCIS) (Gupta et al., 2002). In rare cases, foamy)Tj T* 0.062 Tc 0.063 Tw (apocrine cells may be mistaken for inflammatory)Tj T* 0 Tc 0.108 Tw (reaction with abundant histiocytic proliferation. In such)Tj T* 0.075 Tc 0.068 Tw (cases antibodies to cytokeratins \(e.g. AE1/AE3,)Tj T* 0 Tc 0 Tw (CAM5.2\) may be helpful \(Lakhani et al., 2012\).)Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 9.5 0 0 9.5 46.3543 585.1754 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Steroid receptor profile of apocrine carcinomas)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 63.3543 563.8355 Tm 0 Tr 0 0 0 1 k 0.075 Tc 0.232 Tw (Apocrine epithelium of the breast shows a)Tj -1.61905 -1.01619 TD 0.005 Tc 0.12 Tw (characteristic steroid receptor profile: ER negative, PR)Tj T* 0.055 Tc 0.07 Tw [(negative, and AR positive \(T)71(avassoli et al., 1996;)]TJ T* 0 Tc 0.064 Tw [(Gatalica, 1997; Selim and W)81(ells, 1999; Zagorianakou et)]TJ T* 0.024 Tw [(al., 2006; Gatalica and T)71(awfik, 2006\). AR activation and)]TJ 0 -1.01618 TD 0.026 Tc 0.099 Tw [(signaling is a hallmark of apocrine dif)19(ferentiation in)]TJ 0 -1.01619 TD 0.013 Tc 0.112 Tw [(breast pathology)65(, although AR expression \(along with)]TJ 0 -1.01618 TD 0.037 Tc 0.088 Tw (other steroid receptors\) has been described in other)Tj 0 -1.01619 TD 0.007 Tc 0.118 Tw (breast lesions, particularly in breast carcinomas \(Isola,)Tj T* 0 Tc 0.097 Tw (1993; T)Tj 3.16559 0.00001 TD (avassoli et al., 1996; Gatalica, 1997; Moinfar et)Tj -3.16559 -1.01619 TD 0.045 Tc 0.08 Tw (al., 2003; Rakha et al., 2007; Micello et al., 2010;)Tj T* -0.02 Tc 0 Tw (Castellano et al., 2010; Collins et al., 201)Tj 15.6082 0 TD (1; Hu et al., 201)Tj 6.06632 0 TD (1\).)Tj -20.05547 -1.0162 TD 0.041 Tc 0.084 Tw (Due to the lack of consistent application of the)Tj -1.61905 -1.01619 TD 0.007 Tc 0.118 Tw (morphologic criteria, there is a substantial variation in)Tj T* 0 Tc 0.125 Tw (the reported literature on the status of steroid receptors)Tj T* 0.015 Tc 0.11 Tw (\(ER/PR/AR\) in invasive apocrine carcinoma \(Kaya et)Tj T* 0.013 Tc 0.112 Tw (al., 2008\). Other reasons for discrepancy may include)Tj T* 0.02 Tc 0.105 Tw [(dif)18(ferent cutof)18(f values for positivity and the methods)]TJ T* 0 Tc 0.112 Tw (used for detection of ER and PR as the historic studies)Tj T* 0.069 Tw (were mainly based on the radioimmunoassay for steroid)Tj T* -0.025 Tc 0 Tw (receptor detection (Eusebi et al., 1986; Bundred et al., 1990).)Tj 1.61905 -1.01619 TD 0.012 Tc 0.112 Tw (Of note, other isoforms of full length )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 234.7922 339.7655 Tm 0 Tr 0 0 0 1 k 0.013 Tc 0 Tw (ER-alpha66)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 46.3543 329.0955 Tm 0 Tr 0 0 0 1 k 0 Tc 0.021 Tw (have been described in apocrine carcinomas. W)Tj 19.12167 0 TD -0.0001 Tc (e)Tj 0.71524 0 Td 0 Tc 0 Tw (showed)Tj -19.83691 -1.01619 TD 0.038 Tc 0.087 Tw (the presence of ER-alpha36, a 36 kDa alternatively)Tj T* 0 Tc 0.04 Tw (spliced variant of full )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 140.7289 307.7555 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (ER-alpha66)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 194.5088 307.7555 Tm 0 Tr 0 0 0 1 k 0 Tc 0.04 Tw (gene transcript, in the)Tj -14.10995 -1.01619 TD 0.024 Tc 0.101 Tw (vast majority of invasive apocrine carcinomas of the)Tj T* 0.075 Tc 0.402 Tw [(breast \(V)60(ranic et al., 201)37(1a\). ER-alpha36 is)]TJ T* 0.009 Tc 0.116 Tw (predominantly expressed on the cell membrane and in)Tj T* 0 Tc 0.069 Tw (the cytoplasm of tumor cells and mediates non-genomic)Tj T* 0.063 Tw ((rapid) estrogen signaling through the mitogen-activated)Tj T* 0.032 Tc 0.093 Tw (protein kinase (MAPK/ERK) signaling pathway and)Tj T* 0 Tc 0.016 Tw [(EGFR \(W)80(ang et al., 2006; Zhang et al., 201)38(1\). An earlier)]TJ T* 0.001 Tc 0.124 Tw (study of Bratthauer et al. reported that ER mRNA was)Tj T* 0.029 Tc 0.096 Tw (detectable in apocrine carcinoma despite a complete)Tj T* 0 Tc 0.077 Tw (absence of ER protein using the commercially available)Tj T* 0.068 Tc 0.057 Tw (immunohistochemical assay against ER-alpha 66)Tj T* 0.021 Tc 0.104 Tw ((Bratthauer et al., 2002). The authors studied the ER)Tj T* 0.001 Tc 0.123 Tw (mRNA using primers that covered the first and second)Tj T* 0.035 Tc 0.09 Tw (exon of the )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 103.4532 158.3755 Tm 0 Tr 0 0 0 1 k 0.035 Tc 0 Tw (ER-alpha66)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 161.801 158.3755 Tm 0 Tr 0 0 0 1 k 0.035 Tc 0.09 Tw (messenger RNA and found)Tj -10.99492 -1.01619 TD 0 Tc 0.082 Tw (them to be intact. It is therefore possible that detectable)Tj -0.0001 Tc (ER)' 1.57529 0 Td 0 Tc 0.047 Tw (mRNA in apocrine carcinomas might well be one of)Tj -1.57529 -1.01619 TD 0.076 Tw (the alternatively spliced isoforms of ER-alpha including)Tj T* 0 Tw [(ER-alpha36 \(V)60(ranic et al., 201)38(1a\). )]TJ 1.619 -1.0162 TD 0.031 Tc 0.094 Tw [(Estrogen receptor)20(-beta (ER-beta) which shares a)]TJ -1.619 -1.0162 TD 0.005 Tc 0.12 Tw (high degree of amino acid homology with ER-alpha66)Tj T* 0.01 Tc 0.115 Tw (has been found overexpressed in ER-alpha66 negative)Tj T* 0.075 Tc 0.275 Tw (breast carcinomas including invasive apocrine)Tj T* 0.01 Tc 0.115 Tw (carcinoma of the breast \(Sakamoto and Honma, 2009;)Tj T* 0 Tc 0.109 Tw [(Y)100(an et al., 201)37(1\). Honma et al. showed the presence of)]TJ ET 0 0 0 0 k 307.559 44.774 242.362 644.612 re f BT /F1 1 Tf 10.5 0 0 10.5 308.559 681.2054 Tm 0 0 0 1 k 0.006 Tc 0.119 Tw (ER-beta and ER-beta1 isoforms in apocrine carcinoma)Tj 0 -1.01619 TD 0.024 Tc 0.101 Tw (with beta1 isoform exhibiting a favorable prognostic)Tj T* 0.027 Tc 0.098 Tw (value in invasive apocrine carcinoma \(Honma et al.,)Tj T* 0.018 Tc 0.107 Tw (2007, 2008\). The precise role of ER-beta in apocrine)Tj T* 0 Tc 0 Tw (carcinoma remains to be determined.)Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 9.5 0 0 9.5 308.559 617.1854 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Markers of apocrine differentiation)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 325.559 595.8455 Tm 0 Tr 0 0 0 1 k 0 Tc 0.098 Tw (Androgen receptor (AR) is a member of the steroid)Tj -1.61905 -1.01619 TD 0.006 Tc 0.119 Tw [(receptor family)66(. It is a single polypeptide with various)]TJ 0 -1.01618 TD 0.017 Tc 0.108 Tw [(domains that mediate dif)19(ferent functions \(Gucalp and)]TJ 0 -1.01619 TD 0 Tc 0.11 Tw [(T)35(raina, 2010\). Its activity has been implicated in breast)]TJ T* 0.02 Tc 0.105 Tw (cancer development and progression. AR exerts anti-)Tj T* 0.004 Tc 0.121 Tw [(estrogenic, growth-suppressive ef)18(fects in normal breast)]TJ T* 0 Tc 0.077 Tw (tissue and ER-positive breast carcinomas \(Hickey et al.,)Tj T* 0.037 Tc 0.088 Tw [(2012\). However)39(, in ER-negative breast carcinomas,)]TJ 0 -1.01618 TD 0.061 Tc 0.064 Tw (including invasive apocrine carcinoma, it has the)Tj 0 -1.01619 TD 0.06 Tc 0.065 Tw [(opposite ef)18(fect, promoting cell growth and tumor)]TJ 0 -1.01618 TD 0 Tc 0.108 Tw (development (Hickey et al., 2012). FoxA1 transcription)Tj 0 -1.01619 TD 0.118 Tw (factor appears to be a key mediator of AR signaling in)Tj T* 0.016 Tw (breast cancer)Tj 5.22145 0.00001 TD (,)Tj 0.51579 0 Td (including apocrine carcinoma of the breast)Tj -5.73723 -1.01619 TD (\(Robinson et al., 201)Tj 8.37026 0 TD (1; Dumay et al., 2013\). Naderi et al.)Tj -8.37026 -1.01619 TD 0.016 Tc 0.109 Tw (also found a significant functional cross-talk between)Tj T* 0 Tc 0.103 Tw (AR and HER-2 that involves FoxA1 activity as well as)Tj T* 0.022 Tc (extracellular signal-regulated kinase (ERK) signaling)Tj T* 0 Tc 0.109 Tw (pathway \(Naderi and Hughes-Davies, 2008; Naderi and)Tj T* 0.028 Tw [(Liu, 2010; Naderi et al., 201)38(1; Naderi and Meyer)40(, 2012\).)]TJ T* 0.03 Tc 0.095 Tw [(Moreover)40(, Naderi and Meyer showed that prolactin-)]TJ T* 0.058 Tc 0.067 Tw (induced protein (PIP) (or GCDFP-15) is the most)Tj T* 0 Tc 0.008 Tw (actively regulated gene by the AR/ERK feedback loop in)Tj T* 0 Tw (apocrine tumor cells \(Naderi and Meyer)Tj 15.97926 0 TD -0.0001 Tc (,)Tj 0.49989 0 Td 0 Tc (2012\).)Tj -14.8601 -1.01619 TD 0.012 Tc 0.113 Tw (The expression of AR has been observed in up to)Tj -1.61905 -1.01619 TD 0.034 Tc 0.091 Tw (80% of breast carcinomas including ER-/PR- breast)Tj T* 0.004 Tc 0.121 Tw (carcinomas. The percentage of AR expression in some)Tj T* (subtypes is higher than ER and PR \(up to 90% in low)Tj T* 0 Tc 0.072 Tw (grade invasive ductal carcinomas\) \(Isola, 1993; Moinfar)Tj T* 0.012 Tc 0.113 Tw (et al., 2003; Agof)Tj 7.55884 0 TD 0.0117 Tc (f)Tj 0.71964 0 Td 0.012 Tc (et al., 2003; Miccelo et al., 2010\).)Tj -8.27847 -1.01619 TD 0.045 Tc 0.08 Tw (Owing to its consistent overexpression in apocrine)Tj T* 0.04 Tc 0.085 Tw (epithelium, AR has been designated as an apocrine)Tj T* 0.031 Tc 0.094 Tw [(dif)18(ferentiation marker \(Miller et al., 1985; Gatalica,)]TJ T* 0.017 Tc 0.108 Tw [(1997; Sapp et al., 2003; V)60(ranic et al., 2010\). AR has)]TJ T* 0.034 Tc 0.091 Tw (been associated with HER-2/neu signaling in breast)Tj T* 0.05 Tc 0.074 Tw (cancer \(Moinfar et al., 2003; Micello et al., 2010;)Tj T* 0 Tc 0.089 Tw (Collins et al., 201)Tj 7.31261 0.00001 TD (1\) including special types like Paget\325)Tj 15.19011 0.00001 TD (s)Tj -22.50272 -1.0162 TD 0.008 Tc 0.117 Tw (disease of the breast and apocrine carcinoma \(Diaz de)Tj 0 -1.01619 TD 0 Tc 0.091 Tw (Leon et al., 2000; V)Tj 8.25035 0.00001 TD 0 Tw (ar)Tj 0.75879 0.00001 TD 0.091 Tw (ga et al., 2004; Liegl et al., 2005;)Tj -9.00914 -1.01621 TD 0.012 Tc 0.113 Tw [(Naderi and Hughes-Davies, 2008; V)60(ranic et al., 2010;)]TJ 0 -1.01619 TD 0 Tc 0.093 Tw (Micello et al., 2010; Bhar)Tj 10.62788 0.00001 TD (gava et al., 2010; Neimeier et)Tj -10.62788 -1.01619 TD 0 Tw (al., 2010; Naderi et al., 201)Tj 10.87623 0.00001 TD (1\).)Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 325.559 158.3755 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (AR)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 341.2346 158.3755 Tm 0 Tr 0 0 0 1 k 0 Tc 0.021 Tw (gene mutations have not been described in breast)Tj -3.11196 -1.01619 TD 0.06 Tw (carcinoma tissue samples but a mutation of the )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 513.0194 147.7055 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (AR)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 529.1004 147.7055 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (gene)Tj -21.00394 -1.01619 TD 0.029 Tc 0.096 Tw (has recently been described in an apocrine cell line,)Tj T* 0.075 Tc 0.269 Tw (MDA-MB-453 (Moore et al., 2012). AR gene)Tj T* 0.022 Tc 0.103 Tw (microsatellite polymorphisms and active gene losses,)Tj T* 0.052 Tc 0.073 Tw (which have been described, may contribute to AR)Tj T* 0 Tc 0.045 Tw (protein status in female breast carcinomas with potential)Tj T* 0.005 Tw (implications on tumor initiation and progression \(Shan et)Tj T* 0.07 Tw (al., 2000; Kasami et al., 2000\). Thus, AR immunohisto-)Tj T* 0.001 Tc 0.124 Tw (chemical detection may correlate with CAG repeats on)Tj T* 0 Tc 0.012 Tw (AR gene with a higher number of repeats being linked to)Tj ET 0 0 0 0 k 45.354 729.071 504.567 14.1729 re f 45.354 715.927 504.567 12.002 re f 45.354 689.417 504.567 25.512 re f 45.354 729.071 504.567 14.1729 re f Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.7 0 0 7.7 46.3543 731.757 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (1396)Tj ET 0 0 0 0 k 45.354 715.927 504.567 12.002 re f Q /GS3 gs /GS2 gs q BT /F4 1 Tf 10.5 0 2.23185 10.5 220.6233 719.277 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Apocrine carcinoma of the breast)Tj ET Q endstream endobj 15 0 obj << /Length 11877 >> stream /GS0 gs /GS1 gs q /GS2 gs 0 0 0 0 k 45.354 396.338 242.363 292.589 re f Q /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 46.3543 680.7465 Tm 0 Tr 0 0 0 1 k 0.0167 Tc (a)Tj 0.83562 0 Td 0.017 Tc 0.108 Tw (higher AR expression (Narita et al., 2010). In male)Tj -0.83562 -1.01619 TD 0.029 Tc 0.096 Tw [(breast cancer)40(, AR gene alterations were proposed to)]TJ T* 0 Tc 0.097 Tw (initiate the tumor development, but mutations appear to)Tj 0 -1.01618 TD 0.095 Tw [(be exceedingly rare \(W)81(ooster et al., 1992; Lobaccaro et)]TJ 0 -1.01619 TD 0 Tw (al., 1993; Syrj\212koski et al., 2003\).)Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 63.3543 627.3964 Tm 0 Tr 0 0 0 1 k 0.007 Tc 0.118 Tw [(Gr)36(oss cystic disease fluid pr)37(otein 15)]TJ ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 228.5347 627.3964 Tm 0 Tr 0 0 0 1 k 0.007 Tc 0 Tw ((GCDFP-15),)Tj -17.35051 -1.01619 TD 0.036 Tc 0.089 Tw (identified by Haagensen et al. in 1977, is a 15-kDa)Tj T* 0 Tc 0.039 Tw (protein mapped to chromosome 7. GCDFP-15 acts as an)Tj T* 0.021 Tc 0.104 Tw (aspartyl protease with fibronectin as its substrate. Its)Tj T* 0.075 Tc 0.318 Tw (expression has been associated with apocrine)Tj T* 0 Tc 0.106 Tw [(dif)18(ferentiation, including apocrine carcinoma \(Eusebi et)]TJ T* 0.004 Tw (al., 1986; Mazoujian et al., 1989; Haagensen et al., 1990;)Tj 0 -1.01618 TD 0.007 Tc 0.118 Tw (Pagani et al., 1994; Alexiev et al., 1994; Rakha et al.,)Tj 0 -1.01619 TD 0.008 Tc 0.117 Tw [(2006; Banneau et al., 2010; Naderi and Meyer)41(, 2012\),)]TJ 0 -1.01618 TD 0 Tc 0.015 Tw (although its positivity has been confirmed in other breast)Tj 0 -1.01619 TD 0.005 Tc 0.12 Tw (carcinoma subtypes \(Pagani et al., 1994; Sapino et al.,)Tj T* 0 Tc 0.096 Tw [(2001; Lewis et al., 201)37(1\). However)40(, GCDFP-15 protein)]TJ T* 0.022 Tw (expression appears to be decreased in advanced apocrine)Tj 0 -1.01618 TD 0.003 Tc 0.122 Tw (carcinomas, leading some authors to question GCDFP-)Tj 0 -1.01619 TD 0 Tc 0.005 Tw (15 as a definite marker of apocrine carcinoma \(Honma et)Tj T* 0.044 Tw [(al., 2005\). Similarly)66(, an autopsy based study by Cimino-)]TJ T* 0.049 Tc 0.076 Tw (Mathews et al. demonstrated a gradual loss of AR)Tj T* 0 Tc 0.095 Tw (expression during breast cancer progression from initial)Tj T* 0.006 Tc 0.118 Tw (diagnosis to end-stage metastases \(Cimino-Mathews et)Tj T* 0 Tc 0 Tw (al., 2012\).)Tj 1.61905 -1.01619 TD 0.028 Tw (Celis and colleagues did extensive proteomic studies)Tj -1.61905 -1.01619 TD 0.027 Tc 0.098 Tw (on apocrine carcinomas defining a specific )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 247.3767 403.3265 Tm 0 Tr 0 0 0 1 k 0.027 Tc 0 Tw (apocrine)Tj ET 0 0 0 0 k 307.559 45.399 242.362 643.9871 re f BT /F5 1 Tf 10.5 0 0 10.5 308.559 681.2054 Tm 0 0 0 1 k 0.063 Tc 0.062 Tw [(pr)36(otein signatur)38(e)]TJ ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 396.2005 681.2054 Tm 0 Tr 0 0 0 1 k 0.063 Tc 0.062 Tw (which was analogous to that of)Tj -8.34681 -1.01619 TD 0 Tc 0.052 Tw [(apocrine sweat glands \(Celis et al., 2009\) \(T)71(able 1\). The)]TJ T* 0.055 Tc 0.07 Tw (signature includes markers which are consistently)Tj T* 0.075 Tc 0.09 Tw (expressed \(AR, CD24, 15-PDGH [prostaglandin)Tj T* 0.256 Tw (dehydrogenase], ACMS1 [acyl-CoA synthetase)Tj T* 0 Tc 0.097 Tw (medium-chain family member 1]\), and markers that are)Tj T* 0.108 Tw [(not expressed \(ER-alpha, PR, Bcl-2, GA)111(T)80(A-3\) \(Celis et)]TJ T* 0.01 Tc 0.115 Tw (al., 2008, 2009\). Several additional proteins \(markers\))Tj T* 0 Tc 0.101 Tw (have been shown to be characteristically upregulated in)Tj T* 0.096 Tw (apocrine carcinomas, including psoriasin, S100A9, p53,)Tj 0 -1.01618 TD 0.014 Tc 0.111 Tw (hydroxymethylglutaryl coenzyme A reductase \(HMG-)Tj 0 -1.01619 TD 0.002 Tc 0.123 Tw (CoA reductase\), and cyclooxygenase-2 \(COX-2\) \(Celis)Tj T* 0 Tc 0 Tw (et al., 2006\). )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 325.559 542.4955 Tm 0 Tr 0 0 0 1 k 0.075 Tc 0 Tw [(5alpha-r)37(eductase)]TJ ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 415.3017 542.4955 Tm 0 Tr 0 0 0 1 k 0.075 Tc 0.061 Tw (is an enzyme that converts)Tj -10.16597 -1.01619 TD 0.003 Tc 0.122 Tw (testosterone to the potent androgen dihydrotestosterone)Tj T* 0.075 Tc 0.411 Tw ((DHT). Its expression has been observed in)Tj 0 -1.01618 TD 0.107 Tw (approximately 60% of apocrine carcinomas and)Tj 0 -1.01619 TD 0.338 Tw (correlated with adverse parameters, including)Tj 0 -1.01618 TD 0.016 Tc 0.109 Tw (angiolympathic invasion, higher histologic grade, and)Tj 0 -1.01619 TD 0 Tc 0 Tw (poor clinical outcome (Kasashima et al., 2012).)Tj 1.61905 -1.01619 TD 0.001 Tw (Other markers that have been proposed to be specific)Tj -1.61905 -1.01619 TD 0.028 Tc 0.097 Tw (for apocrine dif)Tj 6.83999 0 TD (ferentiation include )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 473.0984 457.1355 Tm 0 Tr 0 0 0 1 k 0.028 Tc 0 Tw (gama-glutaminyl)Tj -15.67042 -1.01619 TD 0 Tc 0.027 Tw (transferase 1)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 366.8606 446.4655 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (\(GGT)Tj 2.29566 0 TD 0.027 Tw (-1\) \(Banneau et al., 2010; Choi et al.,)Tj -7.84819 -1.0162 TD 0.02 Tc 0.105 Tw (2012; Kim et al., 2012; Cha et al., 2012\) and )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 519.4892 435.7955 Tm 0 Tr 0 0 0 1 k 0.02 Tc 0 Tw (tumor)Tj 2.47045 0 TD 0 Tc (-)Tj -22.55904 -1.01619 TD 0.028 Tc 0.097 Tw [(associated glycopr)37(otein-72)]TJ ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 430.8125 425.1255 Tm 0 Tr 0 0 0 1 k 0.0278 Tc (,)Tj 0.65281 0 Td (a)Tj 0.84681 0 Td 0.028 Tc 0.097 Tw (high molecular weight)Tj -13.14282 -1.01619 TD 0 Tc 0.092 Tw (glycoprotein that appears to be a more sensitive marker)Tj T* 0.009 Tc 0.116 Tw [(of apocrine dif)18(ferentiation than GCDFP-15 \(Honma et)]TJ T* 0 Tc 0 Tw (al., 2006\).)Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 9.5 0 0 9.5 308.559 371.7755 Tm 0 Tr 0 0 0 1 k 0.063 Tc 0.076 Tw (The erbB/HER \(human epidermal growth factor)Tj 0 -1.12316 TD 0 Tc 0 Tw (receptor\) family in apocrine carcinomas)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 325.559 339.7655 Tm 0 Tr 0 0 0 1 k 0.029 Tc 0.096 Tw (The erbB \(HER, human epidermal growth factor)Tj -1.61905 -1.01619 TD 0.056 Tc 0.069 Tw (receptor\) family is composed of four homologous)Tj T* 0.031 Tc 0.094 Tw (transmembrane receptors that mediate growth factor)Tj T* 0.006 Tc 0.119 Tw (cellular signaling. The family includes EGFR \(HER-1,)Tj T* 0.05 Tc 0.075 Tw (ErbB1\), ErbB2 \(HER-2/neu\), ErbB3 \(HER-3\), and)Tj T* 0 Tc 0 Tw (ErbB4 (HER-4) (Foley et al., 2010). )Tj ET Q /GS3 gs /GS2 gs q BT /F4 1 Tf 9.5 0 2.01929 9.5 308.559 265.0755 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Epidermal Growth Factor Receptor (EGFR/HER-1))Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 325.559 243.7355 Tm 0 Tr 0 0 0 1 k 0 Tc 0.123 Tw (EGFR status has been extensively studied in breast)Tj -1.61905 -1.01619 TD 0.037 Tc 0.087 Tw (cancer (Foley et al., 2010). EGFR protein has been)Tj T* 0.03 Tc 0.095 Tw (variably overexpressed in breast carcinoma with the)Tj T* 0.072 Tc 0.053 Tw (highest rate in triple-negative breast carcinomas)Tj T* 0.033 Tc 0.092 Tw ((Masuda et al., 2012). )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 415.2274 201.0556 Tm 0 Tr 0 0 0 1 k 0.033 Tc 0 Tw (EGFR)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 447.3891 201.0556 Tm 0 Tr 0 0 0 1 k 0.033 Tc 0.092 Tw (gene \(on chromosome)Tj -13.22192 -1.01619 TD 0.011 Tc 0.114 Tw [(7p1)37(1.2\) alterations \(amplification and gene mutations\))]TJ T* 0 Tc 0.052 Tw (appear to be rare, particularly gene mutations \(Bhar)Tj 21.00396 0.00001 TD 0 Tw (gava)Tj -21.00396 -1.01619 TD 0.069 Tw (et al., 2005\). In contrast to benign apocrine lesions \(e.g.)Tj T* 0.034 Tw (apocrine metaplasia\), EGFR protein expression has been)Tj T* 0.029 Tw (commonly observed in apocrine carcinomas (up to 60%))Tj T* 0.019 Tc 0 Tw (while )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 336.7973 137.0355 Tm 0 Tr 0 0 0 1 k 0.018 Tc 0 Tw (EGFR)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 368.3371 137.0355 Tm 0 Tr 0 0 0 1 k 0.019 Tc 0.106 Tw (gene alterations \(gene amplification and)Tj -5.69315 -1.01619 TD 0.022 Tc 0.103 Tw (mutations\) appear to be rare \(Feuerhake et al., 2001;)Tj T* 0 Tc 0.003 Tw [(V)60(ranic et al., 2010; Bhar)19(gava et al., 2010; Banneau et al.,)]TJ T* 0.027 Tw [(2010; Alvarenga et al., 2012; Cha et al., 2012; T)72(sutsumi,)]TJ T* 0.042 Tc 0.083 Tw [(2012; W)80(en et al., 2012\). Similar to invasive ductal)]TJ T* 0.001 Tc 0.124 Tw (carcinomas (NST), a substantial proportion of apocrine)Tj T* 0.075 Tc 0.325 Tw (carcinomas also exhibits amplification of the)Tj T* 0.013 Tc 0.112 Tw (centromeric region of chromosome 7 \(detected by the)Tj T* 0.04 Tc 0.085 Tw (chromosome enumeration probe 7, CEP7 polysomy)Tj ET 0 0 0 0 k 45.354 729.071 504.567 14.1729 re f 45.354 716.262 504.567 12 re f Q /GS3 gs /GS2 gs q BT /F4 1 Tf 10.5 0 2.23185 10.5 220.6233 719.6104 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Apocrine carcinoma of the breast)Tj ET 0 0 0 0 k 45.354 689.417 504.567 25.512 re f 45.354 729.071 504.567 14.1729 re f Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.7 0 0 7.7 531.7993 731.757 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (1397)Tj ET 0 0 0 0 k 45.354 47.274 242.363 324.033 re f Q /GS3 gs /GS2 gs q BT /F0 1 Tf 7.5 0 0 7.5 46.3543 364.841 Tm 0 Tr 0 0 0 1 k 0.007 Tc 0.132 Tw (Table 1.)Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 78.8323 364.841 Tm 0 Tr 0 0 0 1 k 0.0072 Tc (A)Tj 1.09095 0 Td 0.007 Tc 0.132 Tw (summary of the most relevant morphologic, immunohisto-)Tj -5.42135 -1.2 TD 0 Tc 0.07 Tw (chemical, cytogenetic, molecular and clinical characteristics of apocrine)Tj T* 0 Tw (carcinoma of the breast.)Tj 0 -2.4 TD (Characteristic)Tj 13.77781 0 TD (Apocrine carcinoma)Tj -13.77781 -2.4 TD (Morphology)Tj 13.77781 0 TD (The presence of the cells with abundant )Tj 0 -1.2 TD (eosinophilic and granular cytoplasm, )Tj T* (centrally to eccentrically located nuclei )Tj T* (with prominent nucleoli and distinctive )Tj T* (cell borders)Tj -13.77781 -1.6 TD (Steroid receptor profile)Tj 13.77781 0 TD (ER-)Tj ET Q /GS3 gs /GS2 gs q BT /F6 1 Tf 7.5 0 0 7.5 162.6005 262.841 Tm 0 Tr 0 0 0 1 k 0 Tc (a)Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 167.332 262.841 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (-, PR-, AR+)Tj -16.13036 -1.6 TD (Specific apocrine markers)Tj 13.77781 0.00001 TD (GCDFP-15+, AR+, GGT-1+, 5)Tj ET Q /GS3 gs /GS2 gs q BT /F6 1 Tf 7.5 0 0 7.5 249.9107 250.841 Tm 0 Tr 0 0 0 1 k 0 Tc (a)Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 254.6421 250.841 Tm 0 Tr 0 0 0 1 k 0 Tc (-)Tj -13.9939 -1.2 TD 0 Tw (reductase+)Tj -13.77781 -1.6 TD [(\322Apocrine protein signature\322)-1446(a\) Positive markers: AR, CD24, 15-)]TJ 13.77781 -1.2 TD (PDGH, ACMS1)Tj T* (b\) Negative markers: ER, PR, Bcl-2, )Tj T* (GATA-3)Tj -13.77781 -1.6 TD (Growth Factor receptors)Tj 13.77781 0.00001 TD (EGFR+/-, HER-2/neu +/-, IGF-1R -)Tj -13.77781 -1.60001 TD (Basal/Myoepithelial Markers)Tj 13.77781 0.00001 TD (Variable positivity for basal cytokeratins )Tj 0 -1.20001 TD ((CK5, CK5/6, CK14, CK17), P-cadherin, )Tj 0 -1.2 TD (and p63 )Tj T* (Negative for CD10, c-Kit (CD117), )Tj T* (CD109 and vimentin)Tj -13.77781 -1.6 TD [(Cytogenetic characteristics)-1834(a\) Gains of 1q, 2q, 1p, 7, and 17)]TJ 13.77781 -1.2 TD (b\) Losses of 1p, 22q, 17q, 12q, and 16q)Tj -13.7778 -1.6 TD (Molecular characteristics)Tj 13.77781 0.00001 TD (\322Molecular apocrine group\322 - increased )Tj 0 -1.20001 TD (AR and HER-2/neu signaling)Tj 0 -1.2 TD (Loss of PTEN gene)Tj T* (Loss of TP53 gene)Tj -13.7778 -1.6 TD (Clinical characteristics)Tj 13.77781 0.00001 TD (Similar to invasive ductal carcinoma )Tj 0 -1.20001 TD ((NST); outcome studies contradictory )Tj 0 -1.2 TD ((see Table 2))Tj ET 0 J 0 j 10 M []0 d 0.567 w 0 0 0 1 K 45.354 339.553 m 287.717 339.553 l S 45.354 323.22 m 287.717 323.22 l S 45.354 47.274 m 287.717 47.274 l S Q endstream endobj 16 0 obj << /Width 918 /ColorSpace/DeviceCMYK /Filter/DCTDecode /Subtype/Image /Height 353 /Type/XObject /Length 228819 /BitsPerComponent 8 >> stream JFIFAdobeeC     C  a }!1AQa"q2#BR$3br %&'()*456789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz w!1AQaq"2B #3Rbr $4%&'()*56789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz??/Qj/^Q~xӣs#Ħ'}\e%};+<_ u?OJ NHJ]6[xJpR*|(>G_>5cu8U "o ^Qn _sk _xQ?F"I h!p̒y[cz Gs_6cO `qBX5H?a_#O.?E6cC `q?BX5G0.?=w_h"?;OK)$w1v/?G@Z>u_'?ᅿX?s_ _k-DO:x b_E4/mG{5AO'`ü?Wj/" s~jw_h"?;OK(4s5_~Co;?? }?'Q|O[ӌ?e? 濘)D,w*E?$Q +i?? 濘)D,w*E?$Q +h6cC `q?BX5@'soe_w_h"?;OK(4G@Z>u_'?9/mG{5A?'`ü?Wj/"~F9w_h"a'Q|O4w?WEG _k-DO;x b_E!_? 濘)D,w*E?$R s~jw_h"?;OK(?w?WE6cC `q?BX5I -j2w_h"?;OK)O+i/mG{5AO'`ü?Wj/"ao#O's5_~Co;?? ?'Q|OW?" 1SG_08X!?,UH[ӌ?e? 濘)D,w*E?$Pao#Ns_Co;?? ?'Q|O s~jw_h"a'Q|O s)_ _k-DO:x b_EF9Ƿ2 1SG_08X!?,UHWI_ _k-DO;x b_E¿FNjw_h"?;OK(?Njw_h"?;OK(4w?eq6cC `q?BX5@$w1v.?=w_h"?;OK(?.jw_h"?;OK(??? 濘'D,w*E?$Q +is5\z? 濘)D,w*E?$Pa_#Np?ໟ" 1SG_08X!?,UH~Fw1v.?=w_h"?;OK(4w?WEG _k-DO:x b_E4S/?G@Zv?_'? _ _k-DO:x b_E¿FNjw_h"?;OK(?t/mG{5AO'`ü?Wj/"a_#N3?E6cC `q?BX5G0/?G@Z>u_'+iOs" 1OGc08X!?,UHW/?G@Z>u_'?8?s_Co;?? }?'Q|O ssk"#/mG{5AO'`ü?Wj/" I?sk" 1SG_08X!?,UHWӟNjw_h"?;OK(?/?G@Z>u_'+i/mG{5AO'`ü?Wj/"a_#O's5_~Co;?? }?'Q|O ;"#/mG{5AO'`ü?Wj/"?k'w1ӿmK'>'' d$}vybHzbU~ϣ\8`eYuOOt<4:*%)4,o#'u9e`t<<*%)N1P}ɵ(Ǔ?wؓEc(uToܯQƝ01q^qЗ|F^%_0?Ի3kA_hOi ]Flc!3J/0H[Ap1UW\|p01^8USzP{G EI8kt xuEn+1>8USzqs].g*O^]Y?b3Gw·_ SܾldȒ# URBEEs.2?CjgI?,grKT31xbQw$EcʝGÃr1#Ec? 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".4?DO)̀?!8cVP?#N8t_*'6,sc_?'St1?+(?qwtxDSca"KY21Y@Yt__J?D_)̀?!>rn>'e05爸}QOc@>R?tW s1?+(qc<OO91TE'YcO'NcVP?#H9??cDSć"KXdD 7? F')8NO\>TOmE?X?P'e@cVQO1爿_K*'6,sd_ Q?B>?XP#N0?loǞ!uQ?c@>R?Br6t~|O?"#W7c?DO)́D ?3~EF9爿]GTOmE?X?P'e@cVP?#H爿]O*'6,scTE/Yc'Gc?cC)1A@>R??B1 ".4y/WO91TE/Yc(#iz1?+(?qwR?"Gc9爿]O*'6,sc_ :#O>L|O_i#xDSca"KXdD ۟?L|OOӏ7x:9}<{*{ F*Z)XUrrMٟ'/m^3XJ8 4%?eV!TT+S7hUvg}_Qo¿c߉rx7-;A_CjzƱ^C V;~mI$vUPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPE endstream endobj 17 0 obj << /Name/Fm5 /BBox[-0.08989 -0.3453 1.08992 3.69007] /Subtype/Form /Resources<>/ProcSet[/PDF/ImageC]/ExtGState<>>> /Type/XObject /Length 35 /Matrix[1 0 0 1 0 0] /OPI<> >> /FormType 1 >> stream /GS1 gs q 1 0 0 1 0 0 cm /Im3 Do Q endstream endobj 18 0 obj << /Name/Fm4 /BBox[0 0 595.27594 782.92896] /Subtype/Form /Resources<>/ProcSet[/PDF]/ExtGState<>>> /Type/XObject /Length 61 /Matrix[1 0 0 1 0 0] /OPI<> >> /FormType 1 >> stream /GS1 gs q 504.55261 0 0 194.0164 45.354 66.9946 cm /Fm5 Do Q endstream endobj 19 0 obj << /Length 9896 >> stream /GS0 gs /GS1 gs q /GS2 gs 0 0 0 0 k 45.354 282.274 242.363 406.653 re f Q /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 46.3543 680.7465 Tm 0 Tr 0 0 0 1 k 0 Tc 0.109 Tw (defined as three or more CEP7 copies in FISH studies\))Tj 0 -1.01619 TD 0.001 Tw [(\()1(V)60(ranic et al., 2010, Grob et al., 2012\). Koletsa et al. also)]TJ T* 0.112 Tw (reported a common )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 134.1523 659.4064 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (CEP7)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 163.039 659.4064 Tm 0 Tr 0 0 0 1 k 0 Tc 0.112 Tw (polysomy in HER-2-positive)Tj -11.11283 -1.01618 TD 0.013 Tc (breast carcinomas but without association with EGFR)Tj 0 -1.01619 TD 0.034 Tc 0.091 Tw (protein status (Koletsa et al., 2010). They found no)Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 46.3543 627.3964 Tm 0 Tr 0 0 0 1 k 0.007 Tc 0 Tw (EGFR)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 77.4093 627.3964 Tm 0 Tr 0 0 0 1 k 0.007 Tc 0.118 Tw (gene amplification but confirmed the activation)Tj -2.95762 -1.01619 TD 0 Tc 0.037 Tw (of EGFR protein through its phosphorylation \(Koletsa et)Tj T* 0.007 Tc 0.118 Tw (al., 2010\). )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 94.9426 606.0564 Tm 0 Tr 0 0 0 1 k 0.007 Tc 0 Tw (CEP7)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 124.2678 606.0564 Tm 0 Tr 0 0 0 1 k 0.007 Tc 0.118 Tw (polysomy has also been described in)Tj -7.42033 -1.01619 TD 0.013 Tc 0.111 Tw (breast carcinomas with EGFR protein overexpression,)Tj T* 0 Tc 0.075 Tw (including triple-negative basal-like breast carcinomas as)Tj T* 0.009 Tw (well as in some special types \(e.g. metaplastic carcinoma)Tj T* 0.034 Tc 0.091 Tw [(of the breast\) \(Gwin et al., 201)37(1; Shao et al., 201)38(1;)]TJ 0 -1.01618 TD 0 Tc 0 Tw (Martin et al., 2012\).)Tj ET Q /GS3 gs /GS2 gs q BT /F4 1 Tf 9.5 0 2.01929 9.5 46.3543 531.3664 Tm 0 Tr 0 0 0 1 k 0.083 Tc 0.454 Tw (Human Epidermal Growth Factor Receptor 2)Tj 0.23873 -1.12316 TD 0 Tc 0 Tw ((erbB2/HER-2/neu) status)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 63.3543 499.3564 Tm 0 Tr 0 0 0 1 k 0 Tc 0.044 Tw [(Her)19(-2/neu protein is overexpressed in approximately)]TJ -1.61905 -1.01618 TD 0.032 Tw (15% of all breast carcinomas (Baehner et al., 2010). The)Tj 0 -1.01619 TD 0.028 Tc 0.097 Tw [(primary mechanism of Her)20(-2/neu activation is )]TJ ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 261.9351 478.0165 Tm 0 Tr 0 0 0 1 k 0.028 Tc 0 Tw (HER-)Tj -20.5315 -1.01619 TD 0 Tc 0.018 Tw (2/neu gene)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 95.1228 467.3465 Tm 0 Tr 0 0 0 1 k 0 Tc 0.018 Tw ((located on 17q12) amplification. In apocrine)Tj -4.64462 -1.01619 TD 0.122 Tw [(carcinoma, the rate of Her)21(-2/neu overexpression \()]TJ ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 262.8146 456.6765 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (HER-)Tj -20.61526 -1.01619 TD 0.074 Tc (2/neu)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 77.5152 446.0065 Tm 0 Tr 0 0 0 1 k 0.074 Tc 0.051 Tw (gene amplification\) is approximately 50%)Tj -2.9677 -1.01619 TD 0 Tc 0.074 Tw (\(between 44% and 54%\) \(Moinfar et al., 2003; V)Tj 20.14289 0 TD 0 Tw (ar)Tj 0.75878 0 TD 0.074 Tw (ga et)Tj -20.90166 -1.0162 TD 0.007 Tc 0.118 Tw (al., 2004; V)Tj 4.97914 0 TD (ranic et al., 2010\) \(Figs. 2D, 3B\) although)Tj -4.97914 -1.01619 TD 0 Tc 0.068 Tw (some studies, on the basis of a limited number of cases,)Tj T* 0.075 Tc 0.075 Tw [(reported a significantly lower rate of Her)21(-2/neu)]TJ T* 0 Tc 0.124 Tw [(positivity \(~17%\) \(W)80(eigelt et al., 2008; Banneau et al.,)]TJ T* 0.032 Tc 0.093 Tw (2010\). Other studies also showed strong association)Tj T* 0.075 Tc 0.544 Tw (between HER-2/neu activation and apocrine)Tj T* 0.004 Tc 0.121 Tw [(dif)18(ferentiation (androgen receptor expression) in breast)]TJ T* 0 Tc 0.074 Tw (cancer \(Farmer et al., 2005; Naderi and Hughes-Davies,)Tj T* 0.091 Tw (2008; Bhar)Tj 4.54436 0 TD [(gava et al., 2009; R)41(yd\216n et al., 2010; Naderi)]TJ -4.54436 -1.01619 TD 0.01 Tc 0.115 Tw (and Liu, 2010; Bhar)Tj 8.57789 0 TD (gava et al., 2010; Niemeier et al.,)Tj -8.57789 -1.01619 TD 0.022 Tc 0.103 Tw (2010; Park et al., 201)Tj 9.42005 0.00001 TD (1; Dumay et al., 2013\). CEP17)Tj -9.42005 -1.01619 TD 0 Tc 0.064 Tw (polysomy (three or more CEP17 copies in FISH assays))Tj T* 0.123 Tw (appears to be a common event in apocrine carcinomas,)Tj T* 0.124 Tw (either as the sole finding or in combination with )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 262.7984 285.9565 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (HER-)Tj ET 0 0 0 0 k 307.559 280.608 242.362 408.319 re f BT /F5 1 Tf 10.5 0 0 10.5 308.559 680.7465 Tm 0 0 0 1 k (2/neu)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 335.0417 680.7465 Tm 0 Tr 0 0 0 1 k 0 Tc 0.05 Tw [(gene amplification \(Schmitt et al., 1998; V)62(ranic et)]TJ -2.52216 -1.01619 TD 0.044 Tc 0.081 Tw (al., 2010\). Several investigators considered CEP17)Tj T* 0.009 Tc 0.116 Tw (polysomy as a potential cause for the equivocal )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 524.7268 659.4064 Tm 0 Tr 0 0 0 1 k 0.009 Tc 0 Tw (HER-)Tj -20.58741 -1.01618 TD 0 Tc (2/neu)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 335.2156 648.7365 Tm 0 Tr 0 0 0 1 k 0 Tc 0.067 Tw [(results by FISH or immunohistochemistry \(Y)100(eh et)]TJ -2.53873 -1.01619 TD 0.02 Tc 0.105 Tw [(al., 2009; Ross, 2010; V)59(ranic et al., 201)38(1b\). Of note,)]TJ T* 0 Tc 0.101 Tw [(Her)19(-2/neu protein expression may also be seen in some)]TJ T* 0.005 Tc 0.12 Tw (benign apocrine lesions such as apocrine adenosis, but)Tj T* 0 Tc 0.011 Tw (without underlying )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 391.6107 606.0564 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (HER-2/neu)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 441.5806 606.0564 Tm 0 Tr 0 0 0 1 k 0 Tc 0.011 Tw (gene alterations \(Selim et)Tj -12.66873 -1.01619 TD 0 Tw (al., 2000\).)Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 9.5 0 0 9.5 308.559 574.0465 Tm 0 Tr 0 0 0 1 k 0.037 Tc 0.102 Tw (Other immunohistochemical markers in apocrine)Tj 0 -1.12316 TD 0 Tc 0 Tw (carcinomas)Tj ET Q /GS3 gs /GS2 gs q BT /F4 1 Tf 9.5 0 2.01929 9.5 308.559 542.0365 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Cytokeratin profile and basal/myoepithelial markers)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 325.559 520.6965 Tm 0 Tr 0 0 0 1 k 0.004 Tc 0.121 Tw (Apocrine carcinomas retain reactivity for epithelial)Tj -1.61905 -1.01619 TD 0.012 Tc 0.113 Tw (markers using immunohistochemical assays, including)Tj T* 0.051 Tc 0.074 Tw (wide-spectrum cytokeratins [CK] (e.g. AE1-AE3),)Tj 0 -1.01618 TD 0.013 Tc 0.112 Tw (luminal cytokeratins including CK7, CK8, CK18, and)Tj 0 -1.01619 TD 0 Tc 0.066 Tw [(CK19, and EMA \(W)79(eigelt et al., 2008; Alvarenga et al.,)]TJ T* 0.058 Tc 0.067 Tw [(201)37(1\). In contrast to most other breast carcinoma)]TJ T* 0.033 Tc 0.092 Tw (subtypes, CK20 positivity has also been reported in)Tj T* 0 Tc 0.079 Tw (breast carcinomas with apocrine dif)Tj 14.57018 0 TD (ferentiation \(Shao et)Tj -14.57018 -1.01619 TD 0.023 Tc 0.102 Tw (al., 2012\). The expression of basal cytokeratins \(e.g.)Tj T* 0.075 Tc 0.155 Tw (CK5, CK5/6, CK14\) is somewhat controversial)Tj T* 0 Tc 0.015 Tw (\(Hasegawa et al., 2008; W)Tj 10.58746 0 TD (eigelt et al., 2008; Bhar)Tj 9.42948 0 TD (gava et)Tj -20.01694 -1.0162 TD 0.06 Tc 0.065 Tw [(al., 2010; V)60(ranic et al., 201)38(1d; Shao et al., 2012;)]TJ 0 -1.01619 TD 0 Tc 0.027 Tw [(Alvarenga et al., 2012; Cha et al., 2012; T)72(sutsumi, 2012;)]TJ T* 0.063 Tc 0.062 Tw [(W)80(en et al., 2012\). The expression of other basal/)]TJ T* 0 Tc 0.041 Tw (myoepithelial markers [e.g. p63, P-cadherin, Insulin-like)Tj T* 0.107 Tw [(growth factor)20(-II mRNA-binding protein 3 (IMP3)] may)]TJ T* 0.023 Tw [(be only sporadically seen \(Hasegawa et al., 2008; V)61(ranic)]TJ T* 0.026 Tc 0.099 Tw (et al., 201)Tj 4.38742 0 TD (1d; Alvarenga et al., 2012\) whereas S-100)Tj -4.38742 -1.01619 TD 0 Tc 0.063 Tw (protein, CD10 \(Neprilysin\), c-Kit \(CD1)Tj 16.09965 0 TD (17\), CD109, and)Tj -16.09965 -1.01619 TD (V)Tj 0.66212 0 TD 0.048 Tw (imentin tend to be negative in the majority of apocrine)Tj -0.66212 -1.01619 TD 0.039 Tw (carcinomas \(W)Tj 6.03895 0.00001 TD (eigelt et al., 2008; Hasegawa et al., 2008\))Tj -6.03895 -1.01619 TD 0.111 Tw [(\(T)70(able 1\). The immunohistochemical profile along with)]TJ T* 0.109 Tw (microarray profiling studies indicates that a majority of)Tj ET 0 0 0 0 k 45.354 729.071 504.567 14.1729 re f 45.354 715.927 504.567 12.002 re f 45.354 689.417 504.567 25.512 re f 45.354 729.071 504.567 14.1729 re f Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.7 0 0 7.7 46.3543 731.757 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (1398)Tj ET 0 0 0 0 k 45.354 715.927 504.567 12.002 re f Q /GS3 gs /GS2 gs q BT /F4 1 Tf 10.5 0 2.23185 10.5 220.6233 719.277 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Apocrine carcinoma of the breast)Tj ET 0 0 0 0 k 45.354 67.677 504.567 193.334 re f /GS3 gs q 45.354 67.677 504.567 193.334 re W n /Fm4 Do Q /GS2 gs 45.354 45.399 504.567 19.4481 re f Q /GS3 gs /GS2 gs q BT /F0 1 Tf 7.5 0 0 7.5 46.3543 58.3811 Tm 0 Tr 0 0 0 1 k 0 Tc 0.036 Tw (Fig. 3. A. )Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 80.4967 58.3811 Tm 0 Tr 0 0 0 1 k 0 Tc 0.036 Tw (Conventional cytogenetics performed on a case of invasive apocrine carcinoma revealed extensive structural and numeric alterations. )Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 7.5 0 0 7.5 529.8975 58.3811 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (B.)Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 539.7494 58.3811 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (An)Tj -65.786 -1.2 TD (interphase Fluorescent in Situ Hybridization (FISH) assay performed on the same case confirmed the presence of the )Tj ET Q /GS3 gs /GS2 gs q BT /F4 1 Tf 7.5 0 1.59418 7.5 437.6672 49.3811 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (HER-2/neu)Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 476.8389 49.3811 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (gene amplification.)Tj ET Q endstream endobj 20 0 obj << /Length 10307 >> stream /GS0 gs /GS1 gs q /GS2 gs 0 0 0 0 k 45.354 44.774 242.363 644.153 re f Q /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 46.3543 680.7465 Tm 0 Tr 0 0 0 1 k 0 Tc 0.097 Tw (apocrine carcinomas, including the triple-negative ones,)Tj 0 -1.01619 TD 0.043 Tw (do not exhibit basal-like phenotype \(Farmer et al., 2005;)Tj T* 0.09 Tw [(W)80(eigelt et al., 2008; Sanga et al., 2009; Ni et al., 201)39(1;)]TJ 0 -1.01618 TD 0 Tw [(V)60(ranic et al., 201)38(1d; Dumay et al., 2013\). )]TJ ET Q /GS3 gs /GS2 gs q BT /F4 1 Tf 9.5 0 2.01929 9.5 46.3543 627.3964 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Insulin-like growth factor receptor 1 (IGF-1R) status)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 63.3543 606.0564 Tm 0 Tr 0 0 0 1 k 0.009 Tc 0.116 Tw (IGF-1R is a transmembrane receptor with tyrosine)Tj -1.61905 -1.01619 TD 0.028 Tc 0.097 Tw (kinase activity whose activation has been associated)Tj T* 0.013 Tc 0.112 Tw (with trastuzumab resistance (Lu et al., 2001). IGF-1R)Tj T* 0.015 Tc 0.11 Tw (appears to be significantly downregulated in apocrine)Tj T* 0 Tc 0.022 Tw (breast lesions including apocrine carcinoma of the breast)Tj 0 -1.01618 TD 0.096 Tw [(as in other ER-negative breast carcinomas \(Bhar)20(gava et)]TJ 0 -1.01619 TD 0 Tw [(al., 201)37(1\).)]TJ ET Q /GS3 gs /GS2 gs q BT /F4 1 Tf 9.5 0 2.01929 9.5 46.3543 520.6964 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Neuroendocrine markers)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 63.3543 499.3564 Tm 0 Tr 0 0 0 1 k 0.046 Tc 0.079 Tw (Apocrine carcinomas are typically negative for)Tj -1.61905 -1.01618 TD 0.075 Tc 0.583 Tw (neuroendocrine markers \(e.g. synaptophysin,)Tj 0 -1.01619 TD 0.006 Tc 0.119 Tw [(c)1(h)1(r)1(o)1(m)1(o)1(g)1(r)1(a)1(n)1(i)1(n)1(-)1(A)1(,)1( )1(C)1(D)1(5)1(6)1(\))1( )1(\()1(W)81(eigelt et al., 2008\). On the)]TJ T* 0.057 Tc 0.068 Tw [(contrary)65(, neuroendocrine carcinomas may express)]TJ T* 0.017 Tc 0.108 Tw (apocrine markers (GCDFP-15) in up to 50% of cases)Tj T* 0 Tc 0 Tw ((Sapino et al, 2001).)Tj ET Q /GS3 gs /GS2 gs q BT /F4 1 Tf 9.5 0 2.01929 9.5 46.3543 424.6665 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Stem cell markers)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 63.3543 403.3265 Tm 0 Tr 0 0 0 1 k 0.024 Tc 0.101 Tw (CD44+/CD24-/low immunophenotype along with)Tj -1.61905 -1.01619 TD 0.022 Tc 0.102 Tw (aldehyde dehydrogenase 1 (ALDH-1) positivity have)Tj T* 0.005 Tc 0.12 Tw (been associated with stem-cell characteristics of breast)Tj T* 0.001 Tc 0.124 Tw (cancer tumor cells (Currie et al., 2013). These markers)Tj T* 0.046 Tc 0.079 Tw (have been described in invasive ductal carcinomas)Tj T* 0.012 Tc 0.112 Tw ((NST) (Currie et al., 2013) as well is in some special)Tj T* 0.057 Tc 0.068 Tw (types, including medullary and metaplastic breast)Tj T* 0 Tc 0.106 Tw (carcinomas (de Be\215a et al., 2013). In contrast, apocrine)Tj T* 0.05 Tc 0.075 Tw (carcinomas do not appear to be enriched with this)Tj T* 0 Tc 0 Tw (immunophenotype (de Be\215a et al., 2013).)Tj ET Q /GS3 gs /GS2 gs q BT /F4 1 Tf 9.5 0 2.01929 9.5 46.3543 285.9565 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Cell cycle markers)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 63.3543 264.6165 Tm 0 Tr 0 0 0 1 k 0 Tc 0.042 Tw (While some of the key cell cycle regulatory proteins)Tj -1.61905 -1.01619 TD 0.004 Tw ((p16, p21, p27, Rb, Cyclin D1, Cyclin A) have been well)Tj T* 0.081 Tw (studied in benign apocrine lesions \(apocrine metaplasia,)Tj T* 0.015 Tc 0.11 Tw (apocrine adenosis\) \(Moriya et al., 2000; Elayat et al.,)Tj T* 0 Tc 0.043 Tw (2009a,b, 201)Tj 5.19971 -0.00001 TD (1\) their role in invasive apocrine carcinoma)Tj -5.19971 -1.01618 TD 0.006 Tw [(remains lar)18(gely unknown. A study of Moriya et al. found)]TJ 0 -1.01619 TD 0.035 Tc 0.09 Tw [(no significant dif)18(fere)1(nce in p21 and p27 expre)-1(ssion)]TJ T* 0 Tc 0.067 Tw (between benign and malignant apocrine lesions \(Moriya)Tj T* 0.005 Tc 0.12 Tw (et al., 2000\). Another flow cytometry study performed)Tj T* 0 Tc 0.05 Tw (on a series of apocrine carcinomas showed an aneuploid)Tj T* 0.014 Tc 0.111 Tw (DNA pattern, a high S-phase fraction and a moderate)Tj T* 0.018 Tc 0.107 Tw (MIB-1 index \(19%\) in apocrine carcinomas \(Gatalica)Tj T* 0 Tc 0.114 Tw [(and T)70(awfik, 2006\). A study on MDA-MB-453 cell line)]TJ T* 0.071 Tc 0.053 Tw (showed a loss of the )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 152.7053 125.9065 Tm 0 Tr 0 0 0 1 k 0.071 Tc 0 Tw (P16-INK4a)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 211.8142 125.9065 Tm 0 Tr 0 0 0 1 k 0.072 Tc 0.053 Tw (gene (at 9p.21))Tj -15.7581 -1.0162 TD 0.011 Tc 0.114 Tw [(followed by the loss of the p16 protein \(V)60(ranic et al.,)]TJ T* 0.024 Tc 0.101 Tw [(201)37(1c\). However)39(, apocrine carcinoma tissue samples)]TJ T* -0.02 Tc 0 Tw (retain p16\(INK4a\) protein expression \(V)Tj 15.48552 0.00001 TD [(ranic et al., 201)38(1c\).)]TJ ET Q /GS3 gs /GS2 gs q BT /F4 1 Tf 9.5 0 2.01929 9.5 46.3543 72.5565 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (C-Myc status)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 63.3543 51.2165 Tm 0 Tr 0 0 0 1 k 0.018 Tc 0.107 Tw (C-MYC gene located at 8q.24 plays an important)Tj ET 0 0 0 0 k 307.559 42.899 242.362 646.028 re f BT /F1 1 Tf 10.5 0 0 10.5 308.559 680.7465 Tm 0 0 0 1 k 0.075 Tc 0.351 Tw (role in various cell functions, including cell)Tj 0 -1.01619 TD 0.005 Tc 0.12 Tw [(proliferation, dif)19(ferentiation, senescence, and apoptosis)]TJ T* 0 Tc 0.06 Tw ((Schmitt and Reis-Filho, 2002). It has been shown to be)Tj 0 -1.01618 TD 0.004 Tc 0.121 Tw (altered in breast carcinomas, particularly in high grade)Tj 0 -1.01619 TD 0 Tc 0.096 Tw (carcinomas \(Selim et al., 2002; Schmitt and Reis-Filho,)Tj T* 0.017 Tc 0.108 Tw [(2002\). Interestingly)65(, c-myc oncoprotein appears to be)]TJ T* 0.041 Tc 0.084 Tw (overexpressed in benign apocrine lesions \(apocrine)Tj T* 0 Tc 0.011 Tw (metaplasia and apocrine adenosis\) without underlying C-)Tj T* 0.051 Tw (MYC gene alterations (Selim et al., 2002). The status of)Tj T* 0.062 Tc 0.063 Tw (C-MYC oncogene in apocrine carcinoma remains)Tj T* 0 Tc 0 Tw (unknown.)Tj ET Q /GS3 gs /GS2 gs q BT /F4 1 Tf 9.5 0 2.01929 9.5 308.559 552.7064 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Neoangiogenesis in apocrine carcinomas)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 325.559 531.3664 Tm 0 Tr 0 0 0 1 k 0.047 Tc 0.078 Tw (Numerous studies confirmed the importance of)Tj -1.61905 -1.01619 TD 0 Tc 0.085 Tw (development of new blood vessels (neoangiogenesis) as)Tj T* 0.014 Tc 0.111 Tw (an essential step in tumor progression and metastasis.)Tj T* 0.046 Tc 0.079 Tw [(Neoangiogenesis in apocrine carcinomas is lar)20(gely)]TJ 0 -1.01618 TD 0.029 Tc 0.096 Tw (unknown, with only one study that included a small)Tj 0 -1.01619 TD 0.025 Tc 0.099 Tw (subset of apocrine carcinomas, although the authors,)Tj T* 0 Tc 0.016 Tw (primarily focusing on invasive ductal carcinomas (NST),)Tj T* 0.05 Tc 0.075 Tw (did not specify the profile of apocrine carcinomas)Tj T* 0 Tc 0 Tw ((Charpin et al., 2004).)Tj ET Q /GS3 gs /GS2 gs q BT /F4 1 Tf 9.5 0 2.01929 9.5 308.559 424.6665 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Autophagy-related proteins status)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 325.559 403.3265 Tm 0 Tr 0 0 0 1 k 0 Tc 0.028 Tw (Autophagy is a component of lysosomal degradation)Tj -1.61905 -1.01619 TD 0.028 Tc 0.097 Tw (and plays an important role in cellular adaptation to)Tj T* 0.008 Tc 0.117 Tw (stress of both normal and malignant cells \(Choi et al.,)Tj T* 0.039 Tc 0.086 Tw (2013\). It is involved in cell survival and cell death)Tj T* 0.075 Tc 0.111 Tw (during cancer progression and cancer treatment)Tj T* 0.034 Tc 0.091 Tw [(\(Rosenfeldt and R)40(yan, 201)37(1\). A study of Kim et al.)]TJ T* 0 Tc 0.073 Tw (indicated that triple-negative apocrine carcinomas \(AR+)Tj T* 0.061 Tc 0.064 Tw (and/or GGT)Tj 5.44577 0 TD (-1+\) overexpressed autophagy-related)Tj -5.44577 -1.01619 TD 0 Tc 0 Tw (proteins, including p62 and beclin-1 (Kim et al., 2012).)Tj ET Q /GS3 gs /GS2 gs q BT /F4 1 Tf 9.5 0 2.01929 9.5 308.559 296.6265 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (TGF-beta family members\325 status)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 325.559 275.2865 Tm 0 Tr 0 0 0 1 k 0.002 Tc 0.123 Tw (Inhibin and activin are two closely related proteins)Tj -1.61905 -1.01619 TD 0.003 Tc 0.122 Tw (with opposite ef)Tj 6.7108 0.00001 TD (fects involved in regulation of follicle-)Tj -6.7108 -1.01619 TD 0.025 Tc 0.1 Tw (stimulating hormone secretion by the pituitary gland)Tj T* 0.064 Tc 0.061 Tw ((Shim et al., 2006). They have been shown to be)Tj T* 0.035 Tc 0.09 Tw (expressed in various tissues, including breast tissue)Tj T* 0 Tc 0.044 Tw ((Shim et al., 2006). A study of Shim et al. indicated that)Tj T* 0.02 Tc 0.105 Tw (inhibin/activin subunits tend to be more expressed in)Tj T* 0.016 Tc 0.109 Tw (apocrine lesions, including apocrine carcinoma of the)Tj T* 0 Tc 0.085 Tw (breast, than in non-apocrine lesions. The precise role of)Tj T* 0.004 Tc 0.121 Tw (inhibin/activin complex in apocrine carcinoma remains)Tj T* 0 Tc 0 Tw (to be elucidated.)Tj ET Q /GS3 gs /GS2 gs q BT /F4 1 Tf 9.5 0 2.01929 9.5 308.559 147.2465 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Aquaporin3 (AQP3) status)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 325.559 125.9065 Tm 0 Tr 0 0 0 1 k 0 Tc 0.051 Tw (AQP3 protein is widely distributed in human tissues)Tj -1.61905 -1.01619 TD 0.124 Tw (and is involved in fluid homeostasis (Niu et al., 2012).)Tj T* 0.028 Tc 0.097 Tw (AQP3 is also involved in cytotoxic activity of some)Tj T* 0.04 Tc 0.085 Tw (chemotherapeutic drugs [capecitabine catabolite 5'-)Tj T* 0.016 Tc 0.109 Tw (deoxy-5-fluorouridine (5'-DFUR) and gemcitabine] in)Tj T* 0.008 Tc 0.117 Tw (the breast cancer cell line MCF-7 \(T)Tj 15.50812 0.00001 TD (rigueros-Motos et)Tj -15.50812 -1.01619 TD 0.025 Tc 0.1 Tw (al., 2012\). It has been shown to be overexpressed in)Tj T* 0.073 Tc 0.052 Tw (various human malignancies, including apocrine)Tj ET 0 0 0 0 k 45.354 729.071 504.567 14.1729 re f 45.354 716.262 504.567 12 re f 45.354 689.417 504.567 25.512 re f 45.354 729.071 504.567 14.1729 re f Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.7 0 0 7.7 531.7993 731.757 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (1399)Tj ET 0 0 0 0 k 45.354 716.262 504.567 12 re f Q /GS3 gs /GS2 gs q BT /F4 1 Tf 10.5 0 2.23185 10.5 220.6233 719.6104 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Apocrine carcinoma of the breast)Tj ET Q endstream endobj 21 0 obj << /Length 12258 >> stream /GS0 gs /GS1 gs q /GS2 gs 0 0 0 0 k 45.354 45.921 242.363 642.381 re f Q /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 46.3543 680.1214 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (carcinoma of the breast (Niu et al., 2012). )Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 9.5 0 0 9.5 46.3543 658.7814 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Cytogenetic characteristics of apocrine carcinoma)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 63.3543 637.4414 Tm 0 Tr 0 0 0 1 k 0.002 Tc 0.123 Tw [(V)111(ery few studies specifically addressed cytogenetic)]TJ -1.61905 -1.01619 TD 0.015 Tc 0.11 Tw (features of apocrine carcinoma. Most of these studies)Tj 0 -1.01618 TD 0.01 Tc 0.115 Tw (included a limited number of cases with contradictory)Tj 0 -1.01619 TD 0.032 Tc 0.093 Tw (results. In contrast to some other special types \(e.g.)Tj T* 0.073 Tc 0.052 Tw (adenoid cystic carcinoma, secretory carcinoma\),)Tj T* 0.061 Tc 0.064 Tw (characteristic translocations specific for apocrine)Tj 0 -1.01618 TD 0.006 Tc 0.119 Tw [(carcinoma have not yet been described \(W)82(eigelt et al.,)]TJ 0 -1.01619 TD 0 Tc 0 Tw (2010a\). )Tj 1.61905 -1.01619 TD -0.0001 Tc (A)Tj 1.09544 0 Td 0 Tc 0.124 Tw (study of Jones et al. showed that apocrine DCIS)Tj -2.71448 -1.01619 TD 0.113 Tw (and invasive apocrine carcinoma frequently show gains)Tj T* 0.009 Tw (of 1q, 2q, 1p, and losses of 1p, 22q, 17q, 12q, and 16q as)Tj T* 0.101 Tw (their most common chromosomal changes \(Jones et al.,)Tj 0 -1.01618 TD 0.016 Tc 0.109 Tw (2001\). Our study based on three apocrine carcinomas)Tj 0 -1.01619 TD 0.075 Tc 0.062 Tw (studied by conventional cytogenetics and single)Tj T* 0.021 Tc 0.104 Tw (nucleotide polymorphism (SNP) array assay revealed)Tj T* 0.001 Tc 0.124 Tw (complex cytogenetic alterations in apocrine carcinomas)Tj T* 0 Tc 0.085 Tw [(with consistent gains of chromosomes 7 and 17 \(V)60(ranic)]TJ T* 0.063 Tc 0.062 Tw (et al., 2010\) \(Fig. 3A\). Conventional cytogenetic)Tj T* 0.075 Tc 0.227 Tw (analysis of MDA-MB-453 cell line revealed a)Tj T* 0 Tc 0.031 Tw (hypertriploid clone characterized by extensive numerical)Tj T* 0.06 Tc 0.065 Tw (and structural abnormalities that include gains of)Tj T* 0.073 Tc 0.052 Tw [(chromosomes 7, 1)37(1, 17, 19 and 21 and losses of)]TJ T* 0 Tc 0.02 Tw (chromosomes X, 3, 4, 9, 13, 14, 16 and 18 \(V)Tj 18.41075 0 TD (ranic et al.,)Tj -18.41075 -1.01619 TD 0.058 Tc 0.067 Tw [(201)37(1c\). Of particular interest is CEP17 polysomy)]TJ T* 0.029 Tc 0 Tw (without )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 84.5298 381.3615 Tm 0 Tr 0 0 0 1 k 0.029 Tc 0 Tw (HER-2/neu)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 138.4689 381.3615 Tm 0 Tr 0 0 0 1 k 0.029 Tc 0.096 Tw (gene amplification \(defined as a)Tj -8.77282 -1.01619 TD 0.025 Tc 0.1 Tw (ratio of )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 84.0319 370.6915 Tm 0 Tr 0 0 0 1 k 0.025 Tc 0 Tw (HER2)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 114.667 370.6915 Tm 0 Tr 0 0 0 1 k 0.025 Tc 0 Tw (to )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 127.2916 370.6915 Tm 0 Tr 0 0 0 1 k 0.025 Tc 0 Tw (CEP17)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 162.8599 370.6915 Tm 0 Tr 0 0 0 1 k 0.0247 Tc (>)Tj 0.96365 0 Td 0.025 Tc 0.1 Tw (2.2\), which is a common)Tj -12.05942 -1.01619 TD 0 Tc 0.043 Tw (event in apocrine carcinoma and may be associated with)Tj T* 0.022 Tc 0 Tw (Her)Tj 1.54612 0 TD 0.103 Tw (-2/neu protein overexpression (scores 2+ and 3+))Tj -1.54612 -1.01619 TD 0 Tc 0.078 Tw (when the absolute )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 127.2398 338.6815 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (HER2)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 156.3405 338.6815 Tm 0 Tr 0 0 0 1 k 0 Tc 0.078 Tw (gene copy number exceeded 6)Tj -10.47488 -1.01619 TD 0 Tw (per nucleus \(V)Tj 5.82593 0 TD (ranic et al., 2010\).)Tj -4.20689 -1.01619 TD 0.037 Tc 0.088 Tw (Another study found a loss of heterozygosity at)Tj -1.61905 -1.01619 TD 0.064 Tc 0.061 Tw (chromosomes 1p35-36 (NB), 3p25 (VHL), 16p13)Tj T* 0.035 Tc 0.09 Tw ((TSC2/PKD1), and 17p13 (TP53) in microdissected)Tj T* 0 Tc 0.019 Tw (apocrine carcinomas of the breast (Lininger et al., 1999).)Tj T* 0.002 Tc 0 Tw (Notably)Tj 3.17011 0.00001 TD 0.0019 Tc (,)Tj 0.62682 0 Td 0.002 Tc 0.123 Tw (several studies found the )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 198.6328 274.6616 Tm 0 Tr 0 0 0 1 k 0.002 Tc 0 Tw (TP53)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 225.4029 274.6616 Tm 0 Tr 0 0 0 1 k 0.002 Tc 0.123 Tw (gene mutation)Tj -17.05225 -1.01619 TD 0.026 Tc 0.099 Tw ((followed by p53 protein overexpression) commonly)Tj T* 0 Tc 0.104 Tw (present in apocrine carcinoma and associated with Her)Tj 22.55888 0.00001 TD (-)Tj -22.55888 -1.0162 TD 0.069 Tw (2/neu overexpression \(Karameris et al., 1995; Moriya et)Tj 0 -1.01619 TD 0.01 Tc 0.115 Tw [(al., 2000; Gatalica and T)71(awfik, 2006; T)70(sutsumi, 2012;)]TJ T* 0 Tc 0.01 Tw [(Dumay et al., 2013\) although T)71(sutsumi (2012) reported a)]TJ T* 0.025 Tc 0.1 Tw (higher p53 protein expression in triple-negative than)Tj T* 0 Tc 0.016 Tw (HER-2/neu positive apocrine carcinomas. A recent study)Tj T* 0.037 Tw (of Dumay et al. confirmed a high frequency of the )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 263.9657 189.3015 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (TP53)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 46.3543 178.6315 Tm 0 Tr 0 0 0 1 k 0 Tc 0.058 Tw (gene mutations in \322molecular apocrine tumors\323 \(defined)Tj 0 -1.01619 TD 0.075 Tc 0.338 Tw (by ER-AR/+/FOX1A+ profile by microarray\),)Tj T* 0.029 Tc 0.095 Tw (particularly non-truncating mutations \(Dumay et al.,)Tj T* 0 Tc 0.06 Tw (2013\). p53 protein expression has also been observed in)Tj T* 0.122 Tw (apocrine DCIS (Leal et al., 2001) in contrast to benign)Tj T* 0 Tw (apocrine lesions (Moriya et al., 2000).)Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 9.5 0 0 9.5 46.3543 103.9415 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Molecular features of apocrine carcinoma)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 63.3543 82.6015 Tm 0 Tr 0 0 0 1 k 0.027 Tc 0.098 Tw (Seminal gene expression profiling studies, based)Tj -1.619 -1.0162 TD 0.02 Tc 0.105 Tw (mainly on the analysis of invasive ductal carcinomas)Tj T* 0 Tc 0.018 Tw ((NST), revealed the existence of five molecular subtypes)Tj T* 0.125 Tw (of breast carcinoma, including luminal subtype \(further)Tj ET 0 0 0 0 k 307.559 44.774 242.362 643.528 re f BT /F1 1 Tf 10.5 0 0 10.5 308.559 680.1214 Tm 0 0 0 1 k 0.073 Tw (subclassified into A and B\), basal-like, normal-like, and)Tj 0 -1.01619 TD 0.002 Tc 0.123 Tw (HER-2 subtype \(Perou et al., 2000; S\277rlie et al., 2001,)Tj T* 0 Tc 0.062 Tw (2003\). Additional gene expression microarray studies of)Tj T* 0.037 Tc 0.088 Tw (breast cancers also discovered a characteristic gene)Tj 0 -1.01618 TD 0.072 Tc 0.053 Tw (expression profile found in apocrine carcinomas)Tj 0 -1.01619 TD 0.044 Tc 0.081 Tw ([\322molecular apocrine group\323] \(Farmer et al., 2005;)Tj 0 -1.01618 TD 0.023 Tc 0.102 Tw (Doane et al., 2006; Kreike et al., 2007; Sanga et al.,)Tj 0 -1.01619 TD 0.017 Tc 0.108 Tw (2009; Guedj et al., 2012; Dumay et al., 2013\). These)Tj T* 0.003 Tc 0.122 Tw [(studies showed that apocrine tumors are dif)19(ferent from)]TJ T* 0.064 Tc 0.06 Tw (common luminal and basal-like breast carcinoma)Tj 0 -1.01618 TD 0.068 Tc 0.057 Tw (subtypes, and are characterized by increased AR)Tj 0 -1.01619 TD 0.075 Tc 0.103 Tw (signaling along with increased )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 467.9263 562.7515 Tm 0 Tr 0 0 0 1 k 0.075 Tc 0 Tw (HER-2/neu)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 526.7383 562.7515 Tm 0 Tr 0 0 0 1 k 0.075 Tc 0 Tw (gene)Tj -20.77898 -1.01619 TD 0 Tc 0.09 Tw (signaling \(Farmer et al., 2005; Sanga et al., 2009; Ni et)Tj T* 0.03 Tc 0.095 Tw [(al., 201)37(1; Dumay et al., 2013\). Ni et al. discovered,)]TJ T* 0 Tc 0.112 Tw (studying the MDA-MB-453 cell line, that AR mediates)Tj T* 0.057 Tw (ligand-dependent activation of Wnt and HER2 signaling)Tj 0 -1.01618 TD 0.003 Tc 0.122 Tw (pathways through transcriptional activation of WNT7B)Tj 0 -1.01619 TD 0.022 Tc 0.103 Tw [(and HER3 \(Ni et al., 201)37(1\). A study of Kreike et al.)]TJ T* 0.002 Tc 0.123 Tw (based on triple-negative apocrine carcinomas identified)Tj T* 0.02 Tc 0.105 Tw (two apocrine clusters: a\) Apocrine-basal gene cluster)Tj T* 0.036 Tc 0.089 Tw (\(EGFR, CLDN1, VLDLR\) and b\) Apocrine-luminal)Tj T* 0.009 Tc 0.116 Tw (gene cluster \(AR, F)Tj 8.26894 0 TD (ASN, MSX2\) that was identical to)Tj -8.26894 -1.01619 TD 0 Tc 0.117 Tw (the \322molecular apocrine group\323 described by Farmer et)Tj T* 0.075 Tc 0.14 Tw [(al. Other authors \(W)80(eigelt et al. 2008\) in their)]TJ T* 0.008 Tc 0.117 Tw (comprehensive study on special histologic subtypes of)Tj T* 0 Tc 0.058 Tw (breast carcinoma showed that apocrine carcinomas \(ER-)Tj T* 0.051 Tc 0.074 Tw (/AR+, GCDFP-15+\) showed a heterogeneous gene)Tj T* 0.042 Tc 0.082 Tw (expression profile pertaining to multiple molecular)Tj T* 0.059 Tc 0.066 Tw (subtypes, although apocrine carcinomas clustered)Tj T* 0.007 Tc 0.118 Tw (together with pleomorphic lobular carcinomas forming)Tj T* 0.015 Tc 0.11 Tw [(\322molecular apocrine\323 signature \(W)82(eigelt et al., 2008\).)]TJ T* 0.044 Tc 0.081 Tw (The study was limited by a small (n=6) number of)Tj T* 0 Tc 0.021 Tw (apocrine carcinomas \(W)Tj 9.73374 0 TD (eigelt et al., 2008\). Robbinson et)Tj -9.73374 -1.01619 TD 0.012 Tc 0.113 Tw (al. study on apocrine cell line model (MDA-MB-453))Tj T* 0.006 Tc 0.119 Tw (showed that AR binds and regulates ER cis-regulatory)Tj T* 0.018 Tc 0.107 Tw (elements in molecular apocrine tumors leading to the)Tj T* 0.032 Tc 0.093 Tw (transcriptional program reminiscent of ER-mediated)Tj T* 0.002 Tc 0.123 Tw (transcription in luminal type carcinomas \(Robbinson et)Tj T* 0 Tc 0.093 Tw (al., 201)Tj 3.02787 0.00001 TD (1\). The reasons for discrepancies that lead some)Tj -3.02787 -1.0162 TD 0.049 Tc 0.076 Tw (investigators to question the existence of apocrine)Tj 0 -1.01619 TD 0.035 Tc 0.09 Tw (carcinoma as a distinct entity may be related to the)Tj T* 0 Tc 0.067 Tw (specific biology of interaction between steroid receptors)Tj T* 0.114 Tw [(ER and AR \(Iggo, 201)37(1\). Iggo \(201)36(1\) summarizing the)]TJ T* 0.012 Tc 0.113 Tw (key findings of Ni et al. and Robinson et al. gives an)Tj T* 0.049 Tc 0.076 Tw (elegant explanation why apocrine carcinomas may)Tj T* 0 Tc 0.022 Tw (exhibit luminal phenotype: \322AR substitutes for ER at the)Tj T* 0.055 Tc 0.07 Tw [(enhancers of ER tar)18(get genes to sustain the broad)]TJ T* 0.042 Tc 0.083 Tw (luminal profile. At the same time, AR binds to the)Tj T* 0 Tc 0.036 Tw (enhancers of a smattering of its own tar)Tj 16.03478 0.00001 TD (get genes to give)Tj -16.03478 -1.01619 TD 0 Tw (the expression profile its apocrine flavor)Tj 16.13184 0.00001 TD (.\323 )Tj -14.51279 -1.0162 TD 0.004 Tc 0.121 Tw [(Importantly)65(, a study of Banneau et al. showed that)]TJ -1.61905 -1.01619 TD 0.075 Tc (patients with a germline mutation of the PTEN)Tj T* 0.063 Tc 0.062 Tw ([Phosphatase and tensin homolog] gene \(Cowden)Tj T* 0 Tc 0.065 Tw (syndrome, OMIM #158350\) are prone to develop breast)Tj T* 0.116 Tw [(carcinomas with apocrine dif)19(ferentiation that also show)]TJ ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 308.559 93.2715 Tm 0 Tr 0 0 0 1 k 0.046 Tc 0 Tw (HER-2/neu)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 364.1262 93.2715 Tm 0 Tr 0 0 0 1 k 0.047 Tc 0.078 Tw (gene activation (Banneau et al., 2010).)Tj -5.29211 -1.01619 TD 0 Tc 0.057 Tw (Furthermore, a gene expression profiling study of breast)Tj T* 0.075 Tc 0.151 Tw (carcinomas developed in patients with Cowden)Tj T* 0.134 Tw (syndrome revealed a significant overlap with a)Tj T* 0.056 Tc 0.069 Tw (\322molecular apocrine carcinoma\323 profile described)Tj ET 0 0 0 0 k 45.354 729.071 504.567 14.1729 re f 45.354 715.927 504.567 12.002 re f 45.354 689.417 504.567 25.512 re f 45.354 729.071 504.567 14.1729 re f Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.7 0 0 7.7 46.3543 731.757 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (1400)Tj ET 0 0 0 0 k 45.354 715.927 504.567 12.002 re f Q /GS3 gs /GS2 gs q BT /F4 1 Tf 10.5 0 2.23185 10.5 220.6233 719.277 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Apocrine carcinoma of the breast)Tj ET Q endstream endobj 22 0 obj << /Length 11554 >> stream /GS0 gs /GS1 gs q /GS2 gs 0 0 0 0 k 45.354 299.566 242.363 388.736 re f Q /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 46.3543 675.5676 Tm 0 Tr 0 0 0 1 k 0.004 Tc 0.121 Tw (previously (Farmer et al., 2005; Banneau et al., 2010).)Tj 0 -1.01619 TD 0 Tc 0.036 Tw (The authors concluded that the activation of the )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 252.3172 664.8976 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (ERBB2-)Tj -19.61551 -1.01619 TD (PI3K-AKT)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 95.0655 654.2276 Tm 0 Tr 0 0 0 1 k 0 Tc 0.112 Tw (signaling axis caused by loss of )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 237.4259 654.2276 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (PTEN)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 266.8957 654.2276 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (gene)Tj -21.00394 -1.01619 TD 0.021 Tc 0.104 Tw (may promote development of breast carcinomas with)Tj T* 0.052 Tc 0.073 Tw [(apocrine dif)18(ferentiation (Banneau et al., 2010). In)]TJ T* 0 Tc 0.02 Tw [(addition, a study of W)80(ang et al. on patients with Cowden)]TJ T* 0.076 Tw (syndrome indicated that )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 152.2428 611.5476 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (PTEN)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 181.3294 611.5476 Tm 0 Tr 0 0 0 1 k 0 Tc 0.076 Tw (gene germline mutations)Tj -12.85477 -1.01618 TD 0.014 Tc 0.11 Tw [(af)18(fect the 3' end of the AR-binding motif resulting in)]TJ 0 -1.01619 TD 0.074 Tc 0.051 Tw (abrogation of androgen-mediated transcriptional)Tj 0 -1.01618 TD 0.025 Tc 0.1 Tw [(activation of PTEN with possibly or)19(gan-specific and)]TJ 0 -1.01619 TD 0.05 Tc 0.075 Tw (sex-specific tumor predisposition in these patients)Tj T* 0 Tc 0.074 Tw [(\(W)80(ang et al., 201)37(1a\). Similarly)66(, a mutation of the )]TJ ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 261.0485 558.1976 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (PTEN)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 46.3543 547.5276 Tm 0 Tr 0 0 0 1 k 0 Tc 0.072 Tw (gene has been described in the apocrine cell line MDA-)Tj 0 -1.01619 TD 0.02 Tw [(MB-453 \(Singh et al., 201)37(1\). Also, a study of Maruyama)]TJ T* 0.001 Tc 0.124 Tw (et al. reported )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 111.0888 526.1876 Tm 0 Tr 0 0 0 1 k 0.001 Tc 0 Tw (PIK3CA)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 150.6812 526.1876 Tm 0 Tr 0 0 0 1 k 0.001 Tc 0.124 Tw (gene mutations in two cases of)Tj -9.9359 -1.01619 TD 0.003 Tc 0.122 Tw (invasive apocrine carcinomas (Maruyama et al., 2007).)Tj T* 0 Tc 0.097 Tw [(T)70(aken together)40(, these studies indicate the importance of)]TJ T* 0.005 Tc 0.12 Tw (deregulation of the PI3K/PTEN/Akt signaling pathway)Tj T* 0 Tc 0 Tw (in the pathogenesis of mammary apocrine carcinoma.)Tj 1.61905 -1.01619 TD 0.062 Tc 0.063 Tw (Although a substantial proportion of apocrine)Tj -1.61905 -1.01619 TD 0 Tc 0.046 Tw (carcinomas are of triple-negative phenotype and the loss)Tj T* 0.005 Tc 0.12 Tw (of PTEN function may be predictive of familial breast)Tj T* 0.006 Tc 0.119 Tw (cancer (Phuah et al., 2012), no study has identified an)Tj T* 0 Tc 0.085 Tw (association between familial breast cancer \(BRCA1 and)Tj T* 0.075 Tc 0.063 Tw (BRCA2 carriers\) and \(strictly defined\) apocrine)Tj T* 0.007 Tc 0.118 Tw (carcinoma. An important negative regulator of )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 254.9465 408.8176 Tm 0 Tr 0 0 0 1 k 0.007 Tc 0 Tw (BRCA1)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 46.3543 398.1476 Tm 0 Tr 0 0 0 1 k 0.013 Tc 0.112 Tw (gene expression, the inhibitor of DNA binding (ID)-4)Tj 0 -1.01619 TD 0 Tc 0.125 Tw ((Id4 protein), appears also to show a negative ef)Tj 20.23857 0 TD (fect in)Tj -20.23857 -1.0162 TD 0.019 Tc 0.106 Tw (triple-negative apocrine carcinomas in contrast to the)Tj 0 -1.01619 TD 0.03 Tc 0.095 Tw (most non-apocrine triple-negative breast carcinomas)Tj T* 0 Tc 0.022 Tw [(\(Rold\207n et al., 2006; W)81(en et al., 2012\). Another negative)]TJ T* 0.035 Tw (regulator of DNA, named Id1 protein, also appears to be)Tj T* 0.021 Tc 0.104 Tw (lower in apocrine carcinomas than in invasive ductal)Tj T* 0 Tc 0 Tw (carcinomas (NST) (Jang et al., 2006).)Tj ET 0 0 0 0 k 307.559 314.357 242.362 373.945 re f Q /GS3 gs /GS2 gs q BT /F0 1 Tf 9.5 0 0 9.5 308.559 675.8247 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Clinical characteristics of apocrine carcinoma)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 325.559 654.4847 Tm 0 Tr 0 0 0 1 k 0.01 Tc 0.115 Tw (Clinical and radiological presentations of apocrine)Tj -1.61905 -1.01619 TD 0.031 Tc 0.094 Tw [(carcinoma do not dif)19(fer from those seen in invasive)]TJ T* 0 Tc 0.009 Tw (ductal carcinomas \(NST\) \(d\325Amore et al., 1988; Gilles et)Tj T* 0.003 Tc 0.122 Tw [(al., 1994; O\325Malley et al., 201)38(1; Lakhani et al., 2012\).)]TJ T* 0.071 Tc 0.054 Tw (Some studies however indicated a higher rate of)Tj 0 -1.01618 TD 0.002 Tc 0.123 Tw (apocrine carcinoma (and AR expression) in the elderly)Tj 0 -1.01619 TD 0 Tc 0.033 Tw [(\(Matsuo et al., 1998, 2002; Honma et al., 2003; Agof)19(f et)]TJ 0 -1.01618 TD 0 Tw (al., 2003\). )Tj 1.61905 -1.01619 TD 0.069 Tw [(Clinically)66(, apocrine carcinomas usually present with)]TJ -1.61905 -1.01619 TD 0.075 Tc 0.101 Tw (palpable tumor mass, rarely with nipple bloody)Tj T* 0 Tc 0.116 Tw [(dischar)18(ge or as a cyst \(Gilles et al., 1994; Mardi et al.,)]TJ T* 0.005 Tw (2004; Lakhani et al., 2012\). Apocrine carcinomas tend to)Tj T* 0.002 Tc 0.123 Tw (be unilateral but are frequently multifocal/ multicentric)Tj T* 0.047 Tc 0 Tw (\(T)Tj 0.96751 0.00001 TD 0.078 Tw (akeuchi et al., 2004; Unal et al., 2007\) although)Tj -0.96751 -1.01619 TD 0 Tc 0.114 Tw (exceptional cases of bilateral apocrine carcinomas have)Tj T* 0.061 Tw [(been described \(Schmitt et al., 1998; W)82(ells and El-A)92(yat,)]TJ T* 0.012 Tc 0.113 Tw (2007\). Metastatic pattern appears to be similar to that)Tj T* 0.051 Tc 0.074 Tw (seen in invasive ductal carcinoma (NST) although)Tj T* 0.013 Tc 0.112 Tw (unusual cases with endometrial polyp metastasis have)Tj T* 0 Tc 0 Tw (been described (Lambot et al., 2001).)Tj 1.61905 -1.01619 TD 0.0025 Tc (A)Tj 1.09948 0 Td 0.003 Tc 0.122 Tw [(gene expression profiling study of W)80(eigelt et al.)]TJ -2.71853 -1.01619 TD 0.006 Tc 0.119 Tw (indicates that \322molecular apocrine\323 carcinomas exhibit)Tj T* 0.039 Tc 0.086 Tw (prognostically poor gene signature with a high-risk)Tj T* 0 Tc 0.046 Tw (recurrence score and a poor 70-gene prognosis signature)Tj T* 0 Tw (\(W)Tj 1.19679 0 TD 0.071 Tw (eigelt et al., 2008\). Apocrine carcinomas also tend to)Tj -1.19679 -1.01619 TD 0.021 Tw (exhibit a high expression of chemokine receptor CXCR4)Tj T* 0.074 Tc 0.051 Tw (that plays an important role in tumor migration,)Tj T* 0 Tc 0 Tw (invasiveness and metastasis (Salvucci et al., 2006).)Tj 1.61905 -1.01619 TD 0.054 Tc 0.07 Tw (Prognosis of patients with apocrine carcinoma)Tj -1.61905 -1.01619 TD 0.05 Tc 0.075 Tw [(remains lar)18(gely unknown as the conducted studies)]TJ T* 0 Tc 0.086 Tw [(recruited a small number of patients \(T)72(able 2\) and have)]TJ T* 0.013 Tc 0.112 Tw (not used well-defined criteria for apocrine carcinoma.)Tj ET 0 0 0 0 k 45.354 729.071 504.567 14.1729 re f 45.354 716.262 504.567 12 re f 45.354 683.748 504.567 31.181 re f 45.354 729.071 504.567 14.1729 re f Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.7 0 0 7.7 531.7993 731.757 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (1401)Tj ET 0 0 0 0 k 45.354 716.262 504.567 12 re f Q /GS3 gs /GS2 gs q BT /F4 1 Tf 10.5 0 2.23185 10.5 220.6233 719.6104 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Apocrine carcinoma of the breast)Tj ET 0 0 0 0 k 45.354 51.023 504.567 226.255 re f Q /GS3 gs /GS2 gs q BT /F0 1 Tf 7.5 0 0 7.5 46.3543 270.8128 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Table 2.)Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 76.3598 270.8128 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Overview of the most relevant clinical studies on apocrine carcinoma)Tj -2.77851 -2.4 TD (Author (year))Tj 13.88825 0 TD (Number of patients)Tj 13.55626 0 TD (Criteria for inclusion)Tj 19.4445 0 TD (Prognosis in comparison with IDC, NST)Tj -46.88902 -2.40003 TD (Frable and Kay (1968))Tj 17.55525 0.00001 TD -0.001 Tc (18)Tj 9.88927 0.00001 TD 0 Tc (In situ and invasive carcinomas)Tj 19.4445 0.00001 TD (Similar prognosis)Tj -46.88902 -1.20002 TD (D\325Amore et al. (1988))Tj 17.55525 0.00001 TD -0.001 Tc (34)Tj 9.88927 0.00001 TD 0 Tc (Invasive carcinoma)Tj 19.4445 0.00001 TD (Similar prognosis)Tj -46.88902 -1.20003 TD (Aoyagi et al. (1990))Tj 17.55525 0.00001 TD -0.001 Tc (10)Tj 9.88927 0.00001 TD 0 Tc (Invasive carcinomas)Tj 19.4445 0.00001 TD (Better prognosis )Tj -46.88902 -1.20003 TD -0.0002 Tc (Abati)Tj 2.55592 0 Td (et)Tj 1.11146 0 Td (al.)Tj 1.33328 0 Td 0 Tc ((1990))Tj 12.55459 0.00001 TD -0.001 Tc (72)Tj 9.88927 0.00001 TD 0 Tc (Both in situ and invasive carcinoma)Tj 19.4445 0.00001 TD (Similar prognosis)Tj -46.88902 -1.20002 TD (Gilles et al. (1994))Tj 17.55525 0.00001 TD -0.001 Tc (17)Tj 9.88927 0.00001 TD 0 Tc (Invasive carcinomas)Tj 19.4445 0.00001 TD (Not given)Tj -46.88902 -1.20003 TD (Matsuo et al. (1998)*)Tj 17.55525 0.00001 TD -0.001 Tc (12)Tj 9.88927 0.00001 TD 0 Tc (In situ and invasive carcinomas*)Tj 19.4445 0.00001 TD (Invasive carcinoma do worse)Tj -46.88902 -1.20002 TD (Takeuchi et al. (2004))Tj 17.55525 0.00001 TD -0.001 Tc (33)Tj 9.88927 0.00001 TD 0 Tc (Invasive carcinomas)Tj 19.4445 0.00001 TD (Similar prognosis )Tj -46.88902 -1.20003 TD (Japaze et al. (2005))Tj 17.55525 0.00001 TD -0.001 Tc (37)Tj 9.88927 0.00001 TD 0 Tc (PAC)Tj 19.4445 0.00001 TD (Better prognosis )Tj -46.88902 -1.20003 TD (Tanaka et al. (2008))Tj 17.55525 0.00001 TD -0.001 Tc (57)Tj 9.88927 0.00001 TD 0 Tc (Invasive carcinomas)Tj 19.4445 0.00001 TD (Similar prognosis)Tj -46.88902 -1.20002 TD (Iwase et al. (2010))Tj 17.55525 0.00001 TD -0.001 Tc (78)Tj 9.88927 0.00001 TD 0 Tc (TN-apocrine carcinomas)Tj 19.4445 0.00001 TD (Better prognosis than non-apocrine)Tj -46.88902 -1.20003 TD (Park et al. (2011))Tj 17.55525 0.00001 TD -0.001 Tc (49)Tj 9.88927 0.00001 TD 0 Tc (MAC)Tj 19.4445 0.00001 TD (Worse prognosis)Tj -46.88902 -1.20002 TD (Cha et al. (2012))Tj 17.55525 0.00001 TD -0.001 Tc (26)Tj 9.88927 0.00001 TD 0 Tc (MAC)Tj 19.4445 0.00001 TD (Similar prognosis)Tj -46.88902 -1.20002 TD (Nagao et al. (2012))Tj 17.8332 0.00001 TD (5)Tj 9.61132 0.00001 TD (Invasive carcinomas)Tj 19.4445 0.00001 TD (Good prognosis)Tj -46.889 -1.2 TD (Choi et al. (2012))Tj 17.55525 0.00001 TD -0.001 Tc (12)Tj 9.88927 0.00001 TD 0 Tc (TN-apocrine carcinomas)Tj 19.4445 0.00001 TD (Better that non-apocrine TNBC)Tj -46.889 -1.2 TD (Montagna et al. (2013))Tj 17.55525 0.00001 TD -0.001 Tc (29)Tj 9.88927 0.00001 TD 0 Tc [(TN apocrine carcinomas)-8613(Similar prognosis)]TJ -27.4445 -1.2 TD (Dellapasqua et al. (2013)*)Tj 17.55525 0.00001 TD -0.001 Tc (72)Tj 9.88927 0.00001 TD 0 Tc [(Invasive carcinomas)-10390(Poor in PAC compared with ALC)]TJ -27.4445 -1.2 TD (Dreyer et al. (2013))Tj 17.55525 0.00001 TD -0.001 Tc (14)Tj 9.88927 0.00001 TD 0 Tc [(TN-apocrine carcinomas)-8558(Similar )]TJ -28.6667 -2.4 TD 0.115 Tw (IDC, NST: Invasive Ductal Carcinoma, no-special-type; PAC: Pure apocrine carcinomas; ALC: Apocrine-like carcinomas; MAC - Molecular apocrine)Tj 0 -1.2 TD 0.024 Tw (carcinomas; TN - Triple-negative carcinomas; TNBC - Triple-negative breast carcinomas. * These studies focused only on apocrine carcinomas \(in situ)Tj T* 0 Tw (and invasive\).)Tj ET 0 J 0 j 10 M []0 d 0.567 w 0 0 0 1 K 45.354 263.094 m 549.921 263.094 l S 45.354 248.428 m 549.921 248.428 l S 45.354 85.606 m 549.921 85.606 l S Q endstream endobj 23 0 obj << /Length 11673 >> stream /GS0 gs /GS1 gs q /GS2 gs 0 0 0 0 k 45.354 44.357 242.363 644.986 re f Q /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 46.3543 681.1631 Tm 0 Tr 0 0 0 1 k 0.075 Tc 0.114 Tw [(Consequently)65(, the available prognostic data are)]TJ 0 -1.01619 TD 0 Tc 0 Tw [(contradictory \(T)71(able 2\).)]TJ 1.61905 -1.01619 TD 0.046 Tc 0.079 Tw (Some studies also indicated a poor response to)Tj -1.61905 -1.01619 TD 0.039 Tc 0.086 Tw (chemotherapy in patients with apocrine carcinomas)Tj T* 0.04 Tc 0.085 Tw ((Nagao et al., 2012), although HER-2/neu enriched)Tj 0 -1.01618 TD 0.052 Tc 0.073 Tw (breast carcinomas tend to have the highest rate of)Tj 0 -1.01619 TD 0.072 Tc 0.053 Tw (complete response to neoadjuvant chemotherapy)Tj 0 -1.01618 TD 0 Tc 0.006 Tw [((Matsubara et al., 2013). Recently)66(, Iizuka et al. described)]TJ 0 -1.01619 TD 0.0374 Tc (a)Tj 0.8564 0 Td 0.037 Tc 0.088 Tw (case of triple-negative apocrine carcinoma with a)Tj -0.8564 -1.01618 TD 0.075 Tc 0.423 Tw (complete pathologic response to neoadjuvant)Tj 0 -1.01619 TD 0 Tc 0 Tw (chemotherapy (Iizuka et al., 2012).)Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 9.5 0 0 9.5 46.3543 553.1232 Tm 0 Tr 0 0 0 1 k 0.022 Tc 0.117 Tw (Targeted therapy options for apocrine carcinoma:)Tj 0 -1.12316 TD 0 Tc 0 Tw (The role of personalized medicine)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 63.3543 521.1133 Tm 0 Tr 0 0 0 1 k 0.003 Tc 0.122 Tw (As a substantial proportion of apocrine carcinomas)Tj -1.61905 -1.01619 TD 0 Tc 0.124 Tw (is HER-2/neu positive, these patients may benefit from)Tj T* 0.07 Tc 0.055 Tw (anti-HER-2/neu therapy and anthracycline-based)Tj T* 0.021 Tc 0.103 Tw (chemotherapy \(Gennari et al, 2008; Fountzilas et al.,)Tj T* 0 Tc 0 Tw (2012\). )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 76.4396 478.4332 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (EGFR)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 106.2276 478.4332 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (and )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 124.3543 478.4332 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (HER-2/neu)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 174.5501 478.4332 Tm 0 Tr 0 0 0 1 k 0 Tc 0.033 Tw (play important roles in the)Tj -12.20912 -1.01619 TD 0.006 Tc 0.119 Tw (pathogenesis of apocrine carcinoma and these findings)Tj T* 0.012 Tc 0.113 Tw (may have significant therapeutic implications, as both)Tj T* 0.075 Tc 0.06 Tw [(tyrosine kinase receptors can be tar)19(geted by the)]TJ T* 0.018 Tc 0.107 Tw [(appropriate drugs. EGFR status in breast cancer)41(, as a)]TJ T* 0.017 Tc 0.108 Tw [(predictor of the response to the EGFR-based tar)19(geted)]TJ T* 0.054 Tc 0.071 Tw (therapy is still not well established; however it is)Tj T* 0.003 Tc 0.122 Tw (important to point out that apocrine carcinomas do not)Tj T* 0 Tc 0.036 Tw (tend to harbor )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 108.9972 393.0732 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (KRAS)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 137.0781 393.0732 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (or )Tj ET Q /GS3 gs /GS2 gs q BT /F5 1 Tf 10.5 0 0 10.5 148.822 393.0732 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (BRAF)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 177.4772 393.0732 Tm 0 Tr 0 0 0 1 k 0 Tc 0.036 Tw [(gene mutations \(V)60(ranic et)]TJ -12.4879 -1.01619 TD 0.009 Tc 0.116 Tw [(al., 201)37(1c\). In regards to HER-2/neu status, the single)]TJ T* 0 Tc 0.103 Tw [(tar)18(geted therapy may not be ef)19(fective and the treatment)]TJ T* 0.028 Tc 0.097 Tw (strategies are now shifting toward a dual anti-HER2)Tj T* 0.015 Tc 0.11 Tw (therapeutic approach \(Konecny)Tj 13.12973 0 TD 0.0146 Tc (,)Tj 0.6396 0 Td 0.015 Tc (2012\). Given that the)Tj -13.76933 -1.01619 TD 0.005 Tc 0.12 Tw (deregulation of the PI3K/PTEN/Akt signaling pathway)Tj T* 0 Tc 0.078 Tw (appears to play an important role in the development of)Tj T* 0.006 Tw [(trastuzumab and lapatinib resistance \(W)82(ang et al., 201)37(1b;)]TJ T* 0.061 Tc 0.064 Tw (Chandarlapaty et al., 2012\) and its importance in)Tj T* 0 Tc 0.006 Tw (apocrine carcinomas \(Maruyama et al., 2007; Banneau et)Tj T* 0.07 Tc 0.055 Tw [(al., 2010; W)80(ang et al., 201)38(1a\), novel therapeutic)]TJ T* 0 Tc 0.125 Tw (strategies that bypass the potential resistance should be)Tj T* 0.006 Tc 0.119 Tw (considered. Thus, a study of Naderi et al. showed that)Tj T* 0.009 Tc 0.116 Tw (the trastuzumab resistance in apocrine carcinomas can)Tj T* 0.015 Tc 0.11 Tw (be successfully overcome by the combined actions of)Tj T* 0.075 Tc 0.061 Tw (AR and MEK inhibitors [MEK is a part of ERK)Tj T* 0 Tc 0.021 Tw (signaling pathway] given that AR regulates ERK (MEK))Tj T* 0.018 Tc 0.107 Tw (phosphorylation via HER-2/neu in apocrine cell lines)Tj T* 0 Tc 0.027 Tw (\(Naderi and Liu, 2010; Naderi et al., 201)Tj 16.47961 0.00001 TD (1\). On the other)Tj -16.47961 -1.0162 TD 0.031 Tc 0.094 Tw (hand, a potential loss of PTEN function in apocrine)Tj 0 -1.01619 TD 0.037 Tc 0.088 Tw (tumor cells may increase their sensitivity to mT)Tj 21.46527 0.00001 TD 0 Tw (OR)Tj -21.46527 -1.01619 TD 0.001 Tc 0.124 Tw (inhibitors (Steelman et al., 2008). A feedback loop has)Tj T* (been demonstrated between AR and ERK where HER-)Tj T* 0 Tc 0.095 Tw (2/neu is activated by AR, while CREB1 \(a downstream)Tj T* 0.019 Tw [(tar)18(get of ERK\) regulates transcription of AR \(Chia et al.,)]TJ T* 0 Tw (201)Tj 1.46313 0.00001 TD (1\).)Tj 0.1559 -1.0162 TD 0.119 Tw (In addition, a consistent AR expression in apocrine)Tj -1.619 -1.0162 TD 0.046 Tc 0.079 Tw (carcinomas could also have a potential therapeutic)Tj T* 0.013 Tc 0.112 Tw (impact. Experimental data from the cell lines indicate)Tj T* 0 Tc 0.03 Tw (that triple-negative breast carcinomas with increased AR)Tj T* 0.048 Tc 0.077 Tw (signaling (= \322molecular apocrine tumors\323) may be)Tj T* 0.075 Tc 0.151 Tw (sensitive to AR antagonists (e.g. bicalutamide))Tj T* 0 Tc 0.125 Tw [(\(Lehmann et al., 201)38(1\). There are also several ongoing)]TJ ET 0 0 0 0 k 307.559 44.357 242.362 644.986 re f BT /F1 1 Tf 10.5 0 0 10.5 308.559 681.1631 Tm 0 0 0 1 k 0.019 Tc 0.106 Tw (and completed clinical trials with antiandrogen drugs)Tj 0 -1.01619 TD 0.035 Tc 0.09 Tw (aimed at treating metastatic and ER-negative breast)Tj T* 0.026 Tc 0.099 Tw [(cancers \(available at: www)66(.clinicaltrials.gov)66(, visited:)]TJ T* 0.016 Tc 0.109 Tw (January 5, 2013\), \(McGhan et al., 2012\). These trials)Tj T* 0.024 Tc 0.101 Tw (should result in definitive guidance in regards to the)Tj 0 -1.01618 TD 0 Tc 0.059 Tw [(ef)18(fects of these drugs in treatment of AR-positive breast)]TJ 0 -1.01619 TD 0 Tw (cancer (McGhan et al., 2012).)Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 9.5 0 0 9.5 308.559 595.8031 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Conclusions)Tj ET Q /GS3 gs /GS2 gs q BT /F1 1 Tf 10.5 0 0 10.5 325.559 574.4632 Tm 0 Tr 0 0 0 1 k 0.006 Tc 0.119 Tw (Apocrine carcinoma of the breast is a rare, special)Tj -1.61905 -1.01619 TD 0 Tc 0.099 Tw (type of breast carcinoma showing distinct morphologic,)Tj T* 0.024 Tc 0.101 Tw (immunophenotypic and molecular features. Apocrine)Tj T* 0 Tc 0.058 Tw (carcinomas are characterized by the apocrine epithelium)Tj T* 0.115 Tw (steroid receptor profile that is ER and PR negative and)Tj 0 -1.01618 TD 0.047 Tc 0.078 Tw (AR positive. The combination of morphologic and)Tj 0 -1.01619 TD 0.03 Tc 0.095 Tw (immunohistochemical criteria (steroid receptors) are)Tj T* 0.059 Tc 0.066 Tw (essential for the proper identification of apocrine)Tj T* 0.03 Tc 0.095 Tw (carcinomas. When these criteria are strictly applied,)Tj T* 0 Tc 0.075 Tw [(apocrine carcinomas express either Her)21(-2/neu or EGFR,)]TJ T* 0.04 Tc 0.085 Tw (which along with AR positivity)Tj 14.08636 0 TD (,)Tj 0.665 0 Td (make the apocrine)Tj -14.75136 -1.01619 TD 0.035 Tc 0.09 Tw (carcinoma patients eligible for the tar)Tj 16.75153 0 TD (geted therapy)Tj 5.89026 0 TD 0 Tc (.)Tj -22.64179 -1.0162 TD 0.075 Tc 0.171 Tw (Clinical outcome of the patients with apocrine)Tj 0 -1.01619 TD 0.002 Tc 0.123 Tw (carcinoma is unclear and further clinical studies, based)Tj T* 0 Tc 0 Tw (on more strict selection criteria, are warranted.)Tj ET Q /GS3 gs /GS2 gs q BT /F4 1 Tf 7.5 0 1.59418 7.5 308.559 403.7432 Tm 0 Tr 0 0 0 1 k 0.015 Tc 0 Tw (Acknowledgements. )Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 380.6882 403.7432 Tm 0 Tr 0 0 0 1 k 0.015 Tc 0.124 Tw (Dr Semir Vranic \(University of Sarajevo, Bosnia)Tj -9.61723 -1.42267 TD 0.04 Tc 0.099 Tw (and Herzegovina\) won a scholarship for post-doc research at the)Tj 0 -1.42266 TD 0.024 Tc 0.115 Tw (University of Turin (Italy) under the Erasmus-Western Balkans joint)Tj 0 -1.42267 TD 0.045 Tc 0.094 Tw (mobility program \(ERAWEB, Erasmus Mundus Action 2 program,)Tj T* 0 Tc 0.078 Tw (Contract Project Reference: 2011-2586-EM Action 2\). Both Universities)Tj T* 0.015 Tc 0.124 Tw (are partners in this project. ERAWEB has been funded with support)Tj T* 0 Tc 0 Tw (from the European Commission. )Tj ET Q /GS3 gs /GS2 gs q BT /F0 1 Tf 9.5 0 0 9.5 308.559 307.7132 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (References)Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 308.559 286.3732 Tm 0 Tr 0 0 0 1 k 0.07 Tc 0.069 Tw (Abati A., Kimmel M. and Rosen P. (1990). Apocrine mammary)Tj 1.65544 -1.42266 TD 0.038 Tc 0.101 Tw (carcinoma. A clinicopathologic study of 72 cases. Am. J. Clin.)Tj 0 -1.42268 TD 0 Tc 0 Tw (Pathol. 94, 371-377.)Tj -1.65544 -1.42267 TD 0.026 Tc 0.113 Tw (Agoff S., Swanson P., Linden H., Hawes S. and Lawton T. (2003).)Tj 1.65544 -1.42267 TD 0 Tc 0.111 Tw (Androgen receptor expression in estrogen receptor-negative breast)Tj 0 -1.42268 TD 0.089 Tw (cancer. Immunohistochemical, clinical, and prognostic associations.)Tj 0 -1.42267 TD 0 Tw (Am. J. Clin. Pathol. 120, 725-731. )Tj -1.65544 -1.42267 TD 0.004 Tc 0.135 Tw (Alexiev B., Boschnakova Z. and Prokopanov C. (1994). The apocrine)Tj 1.65544 -1.42266 TD 0.012 Tc 0.126 Tw (carcinoma of the breast. A cytological, immunohistochemical and)Tj 0 -1.42267 TD 0 Tc 0 Tw (ultrastructural study of 6 cases. Zentralbl. Pathol. 140, 129-134.)Tj -1.65544 -1.42267 TD 0.03 Tc 0.109 Tw (Alvarenga C., Paravidino P., Alvarenga M., Dufloth R., Gomes M.,)Tj 1.65544 -1.42266 TD 0 Tc 0.139 Tw (Zeferino L. and Schmitt F. (2011). Expression of CK19 in invasive)Tj 0 -1.42267 TD 0.118 Tw (breast carcinomas of special histological types: implications for the)Tj T* 0.122 Tw (use of one-step nucleic acid amplification. J. Clin. Pathol. 64, 493-)Tj T* 0 Tw (497.)Tj -1.65544 -1.42266 TD 0.03 Tc 0.109 Tw (Alvarenga C., Paravidino P., Alvarenga M., Gomes M., Dufloth R.,)Tj 1.65544 -1.42268 TD 0.04 Tc 0.099 Tw (Zeferino L., Vassallo J. and Schmitt F. (2012). Reappraisal of)Tj 0 -1.42267 TD 0 Tc 0.064 Tw (immunohistochemical profiling of special histological types of breast)Tj T* 0.02 Tw (carcinomas: a study of 121 cases of eight different subtypes. J. Clin.)Tj T* 0 Tw (Pathol. 65, 1066-1071.)Tj -1.65544 -1.42266 TD 0.004 Tw (Aoyagi H., Ishida T., Yamada I., Kurebayashi J., Kurosumi M., Yokoe T.,)Tj 1.65544 -1.42266 TD 0.097 Tw (Ogawa T., Kawai T. and Izuo M. (1990). Ten cases of an apocrine)Tj 0 -1.42267 TD 0.023 Tc 0.116 Tw (carcinoma of the breast and a review of cases in the Japanese)Tj ET 0 0 0 0 k 45.354 729.071 504.567 14.1729 re f 45.354 715.927 504.567 12.002 re f 45.354 689.417 504.567 25.512 re f 45.354 729.071 504.567 14.1729 re f Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.7 0 0 7.7 46.3543 731.757 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (1402)Tj ET 0 0 0 0 k 45.354 715.927 504.567 12.002 re f Q /GS3 gs /GS2 gs q BT /F4 1 Tf 10.5 0 2.23185 10.5 220.6233 719.277 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Apocrine carcinoma of the breast)Tj ET 0 J 0 j 10 M []0 d 0.567 w 0 0 0 1 K 307.559 416.489 m 549.921 416.489 l S 307.559 332.096 m 549.921 332.096 l S Q endstream endobj 24 0 obj << /Length 12219 >> stream /GS0 gs /GS1 gs q /GS2 gs 0 0 0 0 k 45.354 44.774 242.363 644.612 re f Q /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 58.7701 682.92 Tm 0 Tr 0 0 0 1 k -0.0002 Tc (l)Tj 0.22183 0.00001 TD 0 Tc 0 Tw (iterature. Gan. no. rinsho. 36, 681-689. )Tj -1.87727 -1.42268 TD 0.004 Tw (Arnould N., Pouget O., Gharbi M. and Brettes J.P. (2006). Breast cancer)Tj 1.65544 -1.42266 TD 0.0639 Tc (i)Tj 0.28593 0.00001 TD (n)Tj 1.03667 0 Td 0.064 Tc 0.075 Tw (men: are there similarities with breast cancer in women?)Tj -1.3226 -1.42267 TD 0 Tc 0 Tw (Gyn\216cologie Obst\216trique Fertilit\216 34, 413-419. )Tj -1.65544 -1.42267 TD 0.0415 Tc (B)Tj 0.70853 0.00001 TD (aehner)Tj 3.77897 0 Td 0.042 Tc 0.097 Tw (F., Achacoso N., Maddala T., Shak S., Quesenberry C.,)Tj -2.83206 -1.42267 TD 0.039 Tc 0.1 Tw (Goldstein L., Gown A. and Habel L. (2010). Human epidermal)Tj 0 -1.42266 TD 0.05 Tc (g)Tj 0.60595 0.00001 TD 0.089 Tw (rowth factor receptor 2 assessment in a case-control study:)Tj -0.60595 -1.42268 TD 0.019 Tc 0.12 Tw (comparison of fluorescence in situ hybridization and quantitative)Tj 0 -1.42266 TD 0.045 Tc 0.094 Tw (reverse transcription polymerase chain reaction performed by)Tj -0.0002 Tc (c)' 0.49983 0.00001 TD 0 Tc 0 Tw (entral laboratories. J. Clin. Oncol. 28, 4300-4306. )Tj -2.15527 -1.42266 TD 0.022 Tc 0.117 Tw (Banneau G., Guedj M., MacGrogan G., de Mascarel I., Velasco V.,)Tj 1.65544 -1.42266 TD -0.0002 Tc (S)Tj 0.66684 0.00001 TD 0 Tc 0.076 Tw (chiappa R., Bonadona V., David A., Dugast C., Gilbert-Dussardier)Tj -0.66684 -1.42267 TD 0.06 Tw (B., Ingster O., Vabres P., Caux F., de Reynies A., Iggo R., Sevenet)Tj 0.0832 Tc (N)' 0.80521 0.00001 TD 0.083 Tc 0.208 Tw (., Bonnet F. and Longy M. (2010). Molecular apocrine)Tj -0.80521 -1.42267 TD 0 Tc 0.072 Tw (differentiation is a common feature of breast cancer in patients with)Tj 0 -1.42266 TD 0 Tw (germline PTEN mutations. Breast. Cancer. Res. 12, R63. )Tj -1.65544 -1.42267 TD -0.0001 Tc (B)Tj 0.66686 0.00001 TD 0 Tc 0.058 Tw (hargava R., Gerald W., Li A., Pan Q., Lal P., Ladanyi M. and Chen B.)Tj 0.98858 -1.42267 TD 0.001 Tc 0.138 Tw ((2005). EGFR gene amplification in breast cancer: correlation with)Tj T* 0 Tc 0.056 Tw (epidermal growth factor receptor mRNA and protein expression and)Tj 0 -1.42266 TD 0.0265 Tc (H)Tj 0.74851 0.00001 TD 0.027 Tc 0.112 Tw (ER-2 status and absence of EGFR-activating mutations. Mod.)Tj -0.74851 -1.42268 TD 0 Tc 0 Tw (Pathol. 18, 1027-1033. )Tj -1.65544 -1.42267 TD 0.024 Tw (Bhargava R., Striebel J., Beriwal S., Flickinger J., Onisko A., Ahrendt G.)Tj 1.65544 -1.42267 TD 0.056 Tc 0.083 Tw (and Dabbs D. (2009). Prevalence, morphologic features and)Tj 0 -1.42268 TD 0.015 Tc 0.124 Tw (proliferation indices of breast carcinoma molecular classes using)Tj 0 -1.42267 TD 0 Tc 0.042 Tw (immunohistochemical surrogate markers. Int. J. Clin. Exp. Pathol. 2,)Tj T* 0 Tw (444-455. )Tj -1.65544 -1.42266 TD 0.014 Tw (Bhargava R., Beriwal S., Striebel J. and Dabbs D. (2010). Breast cancer)Tj 1.65544 -1.42267 TD 0.021 Tc 0.118 Tw (molecular class ERBB2: preponderance of tumors with apocrine)Tj 0 -1.42266 TD 0.023 Tc 0.116 Tw (differentiation and expression of basal phenotype markers CK5,)Tj 0 -1.42267 TD 0 Tc 0.062 Tw (CK5/6, and EGFR. Appl. Immunohistochem. Mol. Morphol. 18, 113-)Tj T* 0 Tw (118. )Tj -1.65544 -1.42267 TD 0.049 Tw (Bhargava R., Beriwal S., McManus K. and Dabbs D. (2011). Insulin-like)Tj 1.65544 -1.42267 TD 0.032 Tc 0.106 Tw (growth factor receptor-1 (IGF-1R) expression in normal breast,)Tj T* 0.083 Tc 0.185 Tw (proliferative breast lesions, and breast carcinoma. Appl.)Tj T* 0 Tc 0 Tw (Immunohistochem. Mol. Morphol. 19, 218-225. )Tj -1.65544 -1.42266 TD 0.126 Tw (Bratthauer G., Lininger R., Man Y. and Tavassoli F. (2002). Androgen)Tj 1.65544 -1.42267 TD 0.055 Tw (and estrogen receptor mRNA status in apocrine carcinomas. Diagn.)Tj 0 -1.42266 TD 0 Tw (Mol. Pathol. 11, 113-118. )Tj -1.65544 -1.42268 TD 0.019 Tw (Bryant J. (1981). Male breast cancer: a case of apocrine carcinoma with)Tj 1.65544 -1.42267 TD 0 Tw (psammoma bodies. Hum. Pathol. 12, 751-753. )Tj -1.65544 -1.42268 TD 0.01 Tc 0.129 Tw (Bundred N.J., Stewart H.J., Shaw D.A., Forrest A.P. and Miller W.R.)Tj 1.65544 -1.42266 TD 0.038 Tc 0.101 Tw ((1990). Relation between apocrine differentiation and receptor)Tj 0 -1.42267 TD 0 Tc 0.136 Tw (status, prognosis and hormonal response in breast cancer. Eur. J.)Tj 0 -1.42266 TD 0 Tw (Cancer. 26, 1145-1147.)Tj -1.65544 -1.42267 TD 0.105 Tw (Bundred N., Walker R., Everington D., White G., Stewart H. and Miller)Tj 1.65544 -1.42267 TD 0.059 Tc 0.08 Tw (W. (1990). Is apocrine differentiation in breast carcinoma of)Tj T* 0 Tc 0 Tw (prognostic significance? Br. J. Cancer 62, 113-117.)Tj -1.65544 -1.42266 TD 0.08 Tw (Castellano I., Allia E., Accortanzo V., Vandone A., Chiusa L., Arisio R.,)Tj 1.65544 -1.42267 TD 0.026 Tc 0.112 Tw (Durando A., Donadio M., Bussolati G., Coates A., Viale G. and)Tj T* 0.023 Tc 0.115 Tw (Sapino A. (2010). Androgen receptor expression is a significant)Tj 0 -1.42266 TD 0.038 Tc 0.101 Tw (prognostic factor in estrogen receptor positive breast cancers.)Tj T* 0 Tc 0 Tw (Breast Cancer. Res. Treat. 124, 607-617. )Tj -1.65544 -1.42267 TD 0.134 Tw (Celis J., Gromova I., Gromov P., Moreira J., Cabez\227n T., Friis E. and)Tj 1.6554 -1.4227 TD 0.035 Tw (Rank F. (2006). Molecular pathology of breast apocrine carcinomas:)Tj 0.07 Tc (a)' 1.0428 0 Td 0.069 Tw (protein expression signature specific for benign apocrine)Tj -1.0428 -1.4227 TD 0 Tc 0 Tw (metaplasia. FEBS Lett. 580, 29359-2944.)Tj -1.6554 -1.4227 TD 0.035 Tc 0.104 Tw (Celis J., Gromov P., Cabez\227n T., Moreira J., Friis E., Jirstr\232m K.,)Tj 1.6554 -1.4227 TD 0.068 Tc 0.07 Tw (Llombart-Bosch A., Timmermans-Wielenga V., Rank F. and)Tj T* 0.024 Tc 0.115 Tw (Gromova I. (2008). 15-prostaglandin dehydrogenase expression)Tj T* 0.027 Tc 0.112 Tw (alone or in combination with ACSM1 defines a subgroup of the)Tj ET 0 0 0 0 k 307.559 43.087 242.362 645.84 re f BT /F3 1 Tf 7.5 0 0 7.5 320.9748 682.461 Tm 0 0 0 1 k 0.0682 Tc (a)Tj 0.62418 0.00001 TD 0.068 Tc 0.071 Tw (pocrine molecular subtype of breast carcinoma. Mol. Cell.)Tj -0.62418 -1.42267 TD 0 Tc 0 Tw (Proteomics 7, 1795-1809.)Tj -1.65544 -1.42266 TD -0.0001 Tc (C)Tj 0.72186 0.00001 TD 0 Tc 0.049 Tw (elis J., Cabez\227n T., Moreira J., Gromov P., Gromova I., Timmermans-)Tj 0.93359 -1.42268 TD 0.081 Tw (Wielenga V., Iwase T., Akiyama F., Honma N. and Rank F. (2009).)Tj 0 -1.42266 TD 0.0276 Tc (M)Tj 0.8606 0.00001 TD 0.028 Tc 0.111 Tw (olecular characterization of apocrine carcinoma of the breast:)Tj -0.8606 -1.42267 TD 0 Tc (validation of an apocrine protein signature in a well-defined cohort.)Tj -0.0002 Tc (M)' 0.83283 0.00001 TD 0 Tc 0 Tw (ol. Oncol. 3, 220-237. )Tj -2.48827 -1.42267 TD -0.0002 Tc (C)Tj 0.72184 0.00001 TD 0 Tc 0.059 Tw (ha Y., Jung W.H. and Koo J. (2012). The clinicopathologic features of)Tj 0.9336 -1.42267 TD 0 Tw (molecular apocrine breast cancer. Korean J. Pathol. 46, 169-176. )Tj -1.65544 -1.42267 TD -0.0001 Tc (C)Tj 0.72186 0.00001 TD 0 Tc 0.055 Tw (handarlapaty S., Sakr R., Giri D., Patil S., Heguy A., Morrow M., Modi)Tj 0.93358 -1.42267 TD 0.02 Tc 0.118 Tw (S., Norton L., Rosen N., Hudis C. and King T. (2012). Frequent)Tj 0 -1.42266 TD 0.0203 Tc (M)Tj 0.85327 0.00001 TD 0.02 Tc (utational Activation of the PI3K-AKT Pathway in Trastuzumab-)Tj -0.85327 -1.42268 TD 0 Tc 0 Tw (Resistant Breast Cancer. Clin. Cancer. Res. 18, 6784-6791. )Tj -1.65544 -1.42266 TD -0.0001 Tc (C)Tj 0.72186 0.00001 TD 0 Tc 0.12 Tw (harpin C., Dales J.P., Garcia S., Carpentier S., Djemli A., Andrac L.,)Tj 0.93358 -1.42267 TD 0.083 Tc 0.309 Tw (Lavaut M.N., Allasia C. and Bonnier P. (2004). Tumor)Tj T* 0.027 Tc 0.112 Tw (neoangiogenesis by CD31 and CD105 expression evaluation in)Tj 0 -1.42266 TD 0.0059 Tc (b)Tj 0.56194 0.00001 TD 0.006 Tc 0.133 Tw (reast carcinoma tissue microarrays. Clin. Cancer Res. 10, 5815-)Tj -0.56193 -1.42267 TD 0 Tc 0 Tw (5819.)Tj -1.65544 -1.42266 TD 0.0335 Tc (C)Tj 0.75552 0.00001 TD 0.034 Tc 0.105 Tw (hen Y.Y., Hwang E.S., Roy R., DeVries S., Anderson J., Wa C.,)Tj 0.89992 -1.42268 TD 0.028 Tc 0.111 Tw (Fitzgibbons P., Jacobs T., MacGrogan G., Peterse H., Vincent-)Tj 0 -1.42267 TD 0.042 Tc 0.097 Tw (Salomon A., Tokuyasu T., Schnitt S. and Waldman F. (2009).)Tj T* (Genetic and phenotypic characteristics of pleomorphic lobular)Tj T* 0 Tc 0 Tw (carcinoma in situ of the breast. Am. J. Surg. Pathol. 33, 1683-1694. )Tj -1.65544 -1.42267 TD 0.033 Tc 0.106 Tw (Chia K., Liu J., Francis G. and Naderi A. (2011). A feedback loop)Tj 1.65544 -1.42267 TD 0 Tc 0.02 Tw (between androgen receptor and ERK signaling in estrogen receptor-)Tj T* 0 Tw (negative breast cancer. Neoplasia 13, 154-166. )Tj -1.65544 -1.42267 TD 0.017 Tc 0.121 Tw (Choi J., Jung W.H. and Koo J. (2012). Clinicopathologic features of)Tj 1.65544 -1.42267 TD 0.046 Tc 0.093 Tw (molecular subtypes of triple negative breast cancer based on)Tj T* 0 Tc 0 Tw (immunohistochemical markers. Histol. Histopathol. 27, 1481-1493. )Tj -1.65544 -1.42267 TD 0.003 Tc 0.136 Tw (Choi J., Jung W. and Koo J. (2013). Expression of autophagy-related)Tj 1.65544 -1.42267 TD 0 Tc 0.025 Tw (markers beclin-1, light chain 3A, light chain 3B and p62 according to)Tj T* 0 Tw (the molecular subtype of breast cancer. Histopathology 62, 275-286. )Tj -1.65544 -1.42267 TD 0.139 Tw (Cimino-Mathews A., Hicks J.L., Illei P.B., Halushka M.K., Fetting J.H.,)Tj 1.65544 -1.42267 TD 0.055 Tw (De Marzo A.M., Park B.H. and Argani P. (2012). Androgen receptor)Tj 0 -1.42266 TD 0.097 Tw (expression is usually maintained in initial surgically resected breast)Tj 0 -1.42267 TD 0.117 Tw (cancer metastases but is often lost in end-stage metastases found)Tj 0 -1.42266 TD 0 Tw (at autopsy. Hum. Pathol. 43, 1003-1011)Tj -1.65544 -1.42267 TD 0.098 Tw (Collins L., Cole K., Marotti J., Hu R., Schnitt S. and Tamimi R. (2011).)Tj 1.65544 -1.42267 TD 0.054 Tc 0.084 Tw (Androgen receptor expression in breast cancer in relation to)Tj 0 -1.42268 TD 0.002 Tc 0.137 Tw (molecular phenotype: results from the Nurses\325 Health Study. Mod.)Tj 0 -1.42267 TD 0 Tc 0 Tw (Pathol. 24, 924-931. )Tj -1.65544 -1.42267 TD 0.027 Tc 0.112 Tw (Currie M.J., Beardsley B.E., Harris G.C., Gunningham S.P., Dachs)Tj 1.65544 -1.42266 TD 0 Tc 0.05 Tw (G.U., Dijkstra B., Morrin H.R., Wells J.E. and Robinson B.A. (2013).)Tj T* 0.045 Tc 0.094 Tw (Immunohistochemical analysis of cancer stem cell markers in)Tj 0 -1.42267 TD 0 Tc 0.104 Tw (invasive breast carcinoma and associated ductal carcinoma in situ:)Tj T* 0.009 Tc 0.13 Tw (relationships with markers of tumor hypoxia and microvascularity.)Tj T* 0 Tc 0 Tw (Hum. Pathol. 44, 402-411.)Tj -1.65544 -1.42266 TD 0.061 Tc 0.078 Tw (d\325 Amore E., Terrier-Lacombe M., Travagli J., Friedman S. and)Tj 1.65544 -1.42267 TD 0.004 Tc 0.134 Tw (Contesso G. (1988). Invasive apocrine carcinoma of the breast: a)Tj T* 0 Tc 0.005 Tw (long term follow-up study of 34 cases. Breast Cancer Res. Treat. 12,)Tj 0 -1.42266 TD 0 Tw (37-44. )Tj -1.65544 -1.42266 TD 0.004 Tw (Dag A., Serinsoz E. and Ocal K. (2012). Apocrine carcinoma of the male)Tj 1.65544 -1.42267 TD 0 Tw (breast. Surg. Practice 16:160-163.)Tj -1.65544 -1.42267 TD 0.105 Tw (Damiani S., Cattani M., Buonamici L. and Eusebi V. (1998). Mammary)Tj 1.65544 -1.42267 TD 0.012 Tc 0.126 Tw (foam cells. Characterization by immunohistochemistry and in situ)Tj T* 0 Tc 0 Tw (hybridization. Virchows. Arch. 432, 433-440.)Tj -1.65544 -1.42267 TD 0.034 Tw (de Be\215a F., Caetano P., Gerhard R., Alvarenga C., Gomes M., Paredes)Tj 1.65544 -1.42266 TD 0.139 Tw (J. and Schmitt F. (2013). Cancer stem cells markers CD44, CD24)Tj T* 0.032 Tc 0.107 Tw (and ALDH1 in breast cancer special histological types. J. Clin.)Tj 0 -1.42267 TD 0 Tc 0 Tw (Pathol. 66, 187-191.)Tj ET 0 0 0 0 k 45.354 729.071 504.567 14.1729 re f 45.354 716.262 504.567 12 re f 45.354 689.417 504.567 25.512 re f 45.354 729.071 504.567 14.1729 re f Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.7 0 0 7.7 531.7993 731.757 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (1403)Tj ET 0 0 0 0 k 45.354 716.262 504.567 12 re f Q /GS3 gs /GS2 gs q BT /F4 1 Tf 10.5 0 2.23185 10.5 220.6233 719.6104 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Apocrine carcinoma of the breast)Tj ET Q endstream endobj 25 0 obj << /Length 12418 >> stream /GS0 gs /GS1 gs q /GS2 gs 0 0 0 0 k 45.354 45.399 242.363 643.528 re f Q /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 46.3543 682.461 Tm 0 Tr 0 0 0 1 k 0.015 Tc (D)Tj 0.737 0.00001 TD 0.124 Tw (ellapasqua S., Maisonneuve P., Viale G., Pruneri G., Mazzarol G.,)Tj 0.91844 -1.42267 TD 0 Tc 0.02 Tw (Ghisini R., Mazza M., Iorfida M., Rotmensz N., Veronesi P., Luini A.,)Tj 0 -1.42266 TD 0.0426 Tc (G)Tj 0.82059 0.00001 TD 0.043 Tc 0.096 Tw (oldhirsch A. and Colleoni M. (2013). Immunohistochemically)Tj -0.82059 -1.42268 TD 0.01 Tc 0.128 Tw (Defined Subtypes and Outcome of Apocrine Breast Cancer. Clin.)Tj 0 -1.42266 TD -0.0002 Tc (B)Tj 0.66683 0.00001 TD 0 Tc 0 Tw (reast. Cancer. 13, 95-102.)Tj -2.32227 -1.42267 TD 0.124 Tw (Diaz de Leon E., Carcangiu M., Prieto V., McCue P., Burchette J., To)Tj 1.65544 -1.42267 TD -0.0001 Tc (G)Tj 0.77787 0.00001 TD 0 Tc 0.086 Tw (., Norris B., Kovatich A., Sanchez R., Krigman H. and Gatalica Z.)Tj -0.77787 -1.42267 TD 0.046 Tc (\()Tj 0.37895 0.00001 TD 0.093 Tw (2000\). Extramammary Paget disease is characterized by the)Tj -0.37895 -1.42267 TD 0.067 Tc 0.072 Tw (consistent lack of estrogen and progesterone receptors but)Tj 0.0057 Tc (f)' 0.28375 0.00001 TD 0.006 Tc 0.133 Tw (requently expresses androgen receptor. Am. J. Clin. Pathol. 113,)Tj -0.28375 -1.42267 TD 0 Tc 0 Tw (572-575. )Tj -1.65544 -1.42266 TD -0.0002 Tc (D)Tj 0.72185 0.00001 TD 0 Tc 0.007 Tw (oane A., Danso M., Lal P., Donaton M., Zhang L., Hudis C. and Gerald)Tj 0.93359 -1.42268 TD 0.028 Tc 0.111 Tw (W. (2006). An estrogen receptor-negative breast cancer subset)Tj 0 -1.42266 TD -0.0002 Tc (c)Tj 0.4998 0.00001 TD 0 Tc 0.024 Tw (haracterized by a hormonally regulated transcriptional program and)Tj -0.4998 -1.42267 TD 0 Tw (response to androgen. Oncogene 25, 3994-4008. )Tj -1.65544 -1.42267 TD 0.099 Tw (Dreyer G., Vandorpe T., Smeets A., Forceville K., Brouwers B., Neven)Tj 1.65544 -1.42266 TD 0.0765 Tc (P)Tj 0.74354 0.00001 TD 0.077 Tc 0.062 Tw (., Janssens H., Deraedt K., Moerman P., Van Calster B.,)Tj -0.74354 -1.42267 TD 0.044 Tc 0.095 Tw (Christiaens M.R., Paridaens R. and Wildiers H. (2013). Triple)Tj 0 -1.42266 TD 0.0393 Tc (n)Tj 0.59532 0.00001 TD 0.039 Tc 0.099 Tw (egative breast cancer: Clinical characteristics in the different)Tj -0.59531 -1.42268 TD 0 Tc 0 Tw (histological subtypes. Breast (in press).)Tj -1.65544 -1.42267 TD 0.012 Tc 0.126 Tw (Dumay A., Feugeas J.P., Wittmer E., Lehmann-Che J., Bertheau P.,)Tj 1.65544 -1.42267 TD 0.017 Tc 0.122 Tw (Espi\216 M., Plassa L.F., Cottu P., Marty M., Andr\216 F., Sotiriou C.,)Tj T* 0 Tc 0.04 Tw (Pusztai L. and de Th\216 H. (2013). Distinct tumor protein p53 mutants)Tj T* 0 Tw (in breast cancer subgroups. Int. J. Cancer 132, 1227-1231. )Tj -1.65544 -1.42267 TD 0.077 Tw (Durham J. and Fechner R. (2000). The histologic spectrum of apocrine)Tj 1.65544 -1.42267 TD 0 Tw (lesions of the breast. Am. J. Clin. Pathol. 113, S3-S18. )Tj -1.65544 -1.42267 TD 0.011 Tc 0.128 Tw (Elayat G., Selim A.G.A. and Wells C. (2009a). Alterations of the cell)Tj 1.65544 -1.42267 TD 0.029 Tc 0.11 Tw (cycle regulators cyclin D1, cyclin A, p27, p21, p16, and pRb in)Tj T* 0 Tc 0 Tw (apocrine metaplasia of the breast. Breast J. 15, 475-482.)Tj -1.65544 -1.42267 TD 0.029 Tw (Elayat G., Selim A.G. and Wells C.A. (2009b). Cell cycle alterations and)Tj 1.65544 -1.42267 TD 0.099 Tw (their relationship to proliferation in apocrine adenosis of the breast.)Tj T* 0 Tw (Histopathology 54, 348-354.)Tj -1.65544 -1.42267 TD 0.08 Tw (Elayat G., Selim A.G.A., Gorman P., Tomlinson I. and Wells C. (2011).)Tj 1.65544 -1.42267 TD 0.031 Tc 0.107 Tw (Cyclin D-1 protein over-expression is not associated with gene)Tj 0 -1.42266 TD 0 Tc 0.138 Tw (amplification in benign and atypical apocrine lesions of the breast.)Tj 0 -1.42267 TD 0 Tw (Pathol. Res. Pract. 207, 75-78.)Tj -1.65544 -1.42266 TD 0.004 Tc 0.135 Tw (Elston C. and Ellis I. (1991). Pathological prognostic factors in breast)Tj 1.65544 -1.42267 TD 0.07 Tc 0.068 Tw (cancer. I. The value of histological grade in breast cancer:)Tj T* 0.083 Tc 0.23 Tw (experience from a large study with long-term follow-up.)Tj 0 -1.42268 TD 0 Tc 0 Tw (Histopathology 19, 403-410.)Tj -1.65544 -1.42267 TD 0.03 Tc 0.108 Tw (Eusebi V., Betts C., Haagensen D., Gugliotta P., Bussolati G. and)Tj 1.65544 -1.42267 TD 0 Tc 0.076 Tw (Azzopardi J. (1984). Apocrine differentiation in lobular carcinoma of)Tj 0 -1.42266 TD 0.008 Tc 0.131 Tw (the breast: a morphologic, immunologic, and ultrastructural study.)Tj T* 0 Tc 0 Tw (Hum. Pathol. 15, 134-140. )Tj -1.65544 -1.42267 TD 0.135 Tw (Eusebi V., Millis R., Cattani M., Bussolati G. and Azzopardi J. (1986).)Tj 1.65544 -1.42267 TD 0.083 Tc 0.38 Tw (Apocrine carcinoma of the breast. A morphologic and)Tj T* 0 Tc 0 Tw (immunocytochemical study. Am. J. Pathol. 123, 532-541. )Tj -1.65544 -1.42266 TD 0.037 Tc 0.101 Tw (Eusebi V., Magalhaes F. and Azzopardi J.G. (1992). Pleomorphic)Tj 1.65544 -1.42267 TD 0.039 Tc 0.1 Tw (lobular carcinoma of the breast: an aggressive tumor showing)Tj T* 0 Tc 0 Tw (apocrinedifferentiation. Hum. Pathol. 23, 655-662.)Tj -1.65544 -1.42266 TD 0.013 Tc 0.126 Tw (Farmer P., Bonnefoi H., Becette V., Tubiana-Hulin M., Fumoleau P.,)Tj 1.65544 -1.42266 TD 0 Tc 0.138 Tw (Larsimont D., Macgrogan G., Bergh J., Cameron D., Goldstein D.,)Tj 0 -1.42267 TD 0.051 Tw (Duss S., Nicoulaz A.L., Brisken C., Fiche M., Delorenzi M. and Iggo)Tj T* 0.015 Tc 0.124 Tw (R. (2005). Identification of molecular apocrine breast tumours by)Tj T* 0 Tc 0 Tw (microarray analysis. Oncogene 24, 4660-4671. )Tj -1.6554 -1.4227 TD 0.017 Tc 0.121 Tw (Feuerhake F., Unterberger P. and H\232fter E. (2001). Cell turnover in)Tj 1.6554 -1.4227 TD 0.036 Tc 0.103 Tw (apocrine metaplasia of the human mammary gland epithelium:)Tj T* 0 Tc 0.13 Tw (apoptosis, proliferation, and immunohistochemical detection of Bcl-)Tj T* 0.006 Tc 0.133 Tw (2, Bax, EGFR, and c-erbB2 gene products. Acta Histochem. 103,)Tj T* 0 Tc 0 Tw (53-65. )Tj ET 0 0 0 0 k 307.559 45.399 242.362 643.528 re f BT /F3 1 Tf 7.5 0 0 7.5 308.559 682.461 Tm 0 0 0 1 k 0.0038 Tc (F)Tj 0.61478 0.00001 TD 0.004 Tc 0.135 Tw (oley J., Nickerson N., Nam S., Allen K., Gilmore J., Nephew K. and)Tj 1.04066 -1.42267 TD 0 Tc 0.06 Tw (Riese D. (2010). EGFR signaling in breast cancer: bad to the bone.)Tj 0 -1.42266 TD -0.0002 Tc (S)Tj 0.66683 0.00001 TD 0 Tc 0 Tw (emin. Cell. Dev. Biol. 21, 951-960. )Tj -2.32227 -1.42268 TD 0.11 Tw (Fountzilas G., Dafni U., Bobos M., Batistatou A., Kotoula V., Trihia H.,)Tj 1.65544 -1.42266 TD 0.0549 Tc (M)Tj 0.88789 0.00001 TD 0.055 Tc 0.084 Tw (alamou-Mitsi V., Miliaras S., Chrisafi S., Papadopoulos S.,)Tj -0.88789 -1.42267 TD 0 Tc 0.099 Tw (Sotiropoulou M., Filippidis T., Gogas H., Koletsa T., Bafaloukos D.,)Tj -0.0001 Tc (T)' 0.61087 0.00001 TD 0 Tc 0.086 Tw (elevantou D., Kalogeras K., Pectasides D., Skarlos D., Koutras A.)Tj -0.61087 -1.42267 TD 0.0832 Tc (a)Tj 0.6392 0.00001 TD 0.083 Tc 0.43 Tw (nd Dimopoulos M.A. (2012). Differential response of)Tj -0.6392 -1.42267 TD 0.056 Tw (immunohistochemically defined breast cancer subtypes to)Tj 0.0668 Tc (a)' 0.62278 0.00001 TD 0.067 Tc 0.072 Tw (nthracycline-based adjuvant chemotherapy with or without)Tj -0.62279 -1.42267 TD 0 Tc 0 Tw (paclitaxel. PloS One 7, e37946. )Tj -1.65544 -1.42266 TD -0.0002 Tc (F)Tj 0.61084 0.00001 TD 0 Tc 0.12 Tw (rable W. and Kay S. (1968). Carcinoma of the breast. Histologic and)Tj 1.04461 -1.42268 TD 0 Tw (clinical features of apocrine tumors. Cancer 21, 756-763.)Tj -1.65544 -1.42266 TD 0.0114 Tc (G)Tj 0.7894 0.00001 TD 0.011 Tc 0.127 Tw (atalica Z. (1997). Immunohistochemical analysis of apocrine breast)Tj 0.86604 -1.42267 TD 0.083 Tc 0.094 Tw (lesions. Consistent over-expression of androgen receptor)Tj T* 0 Tc 0.055 Tw (accompanied by the loss of estrogen and progesterone receptors in)Tj 0 -1.42266 TD 0.0088 Tc (a)Tj 0.56485 0.00001 TD 0.009 Tc 0.13 Tw (pocrine metaplasia and apocrine carcinoma )Tj ET Q /GS3 gs /GS2 gs q BT /F4 1 Tf 7.5 0 1.59418 7.5 480.0442 511.741 Tm 0 Tr 0 0 0 1 k 0.0089 Tc (i)Tj 0.23088 0.00001 TD (n)Tj 0.9816 0 Td 0.009 Tc 0 Tw (situ)Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 501.0787 511.741 Tm 0 Tr 0 0 0 1 k 0.0089 Tc (.)Tj 0.7037 0.00001 TD 0.009 Tc 0.13 Tw (Pathol. Res.)Tj -24.71755 -1.42267 TD 0 Tc 0 Tw (Pract. 193, 753-758.)Tj -1.65544 -1.42266 TD 0.0233 Tc (G)Tj 0.80128 0.00001 TD 0.023 Tc 0.115 Tw (atalica Z. and Tawfik O. (2006). Pure apocrine carcinomas of the)Tj 0.85416 -1.42268 TD 0 Tc 0.071 Tw (breast are characterized by consistent aneuploidy, high proliferative)Tj 0 -1.42267 TD 0.016 Tw (fraction and overexpression of Her-2 and p53. Mod. Pathol. 19, 27A.)Tj T* 0 Tw ((Abstract))Tj -1.65544 -1.42267 TD 0.014 Tw (Gennari A., Sormani M., Pronzato P., Puntoni M., Colozza M., Pfeffer U.)Tj 1.65544 -1.42267 TD 0.064 Tc 0.075 Tw (and Bruzzi P. (2008). HER2 status and efficacy of adjuvant)Tj T* 0.073 Tc 0.066 Tw (anthracyclines in early breast cancer: a pooled analysis of)Tj T* 0 Tc 0 Tw (randomized trials. J. Natl. Cancer Inst. 100, 14-20.)Tj -1.65544 -1.42267 TD 0.026 Tc 0.113 Tw (Gerhard R., Costa J. and Schmitt F. (2012). Benign and malignant)Tj 1.65544 -1.42267 TD 0.019 Tc 0.12 Tw (apocrine lesions of the breast. Expert Rev. Anticancer Ther. 12,)Tj T* 0 Tc 0 Tw (215-221. )Tj -1.65544 -1.42267 TD 0.057 Tc 0.082 Tw (Gilles R., Lesnik A., Guinebreti\217re J., Tardivon A., Masselot J.,)Tj 1.65544 -1.42267 TD 0 Tc 0.08 Tw (Contesso G. and Vanel D. (1994). Apocrine carcinoma: clinical and)Tj T* 0 Tw (mammographic features. Radiology 190, 495-497. )Tj -1.65544 -1.42267 TD 0.066 Tc 0.072 Tw (Grekou A., Stravoravdi P., Patakiouta F. and Toliou T. (1999).)Tj 1.65544 -1.42267 TD 0 Tc 0.055 Tw (Intranuclear helioid inclusions in a case of breast carcinoma. Breast)Tj 0 -1.42266 TD 0 Tw (J. 5, 63-64. )Tj -1.65544 -1.42267 TD 0.127 Tw (Grob T., Heilenk\232tter U., Geist S., Paluchowski P., Wilke C., Jaenicke)Tj 1.65544 -1.42266 TD 0.055 Tw (F., Quaas A., Wilczak W., Choschzick M., Sauter G. and Lebeau A.)Tj 0 -1.42267 TD 0.049 Tw ((2012). Rare oncogenic mutations of predictive markers for targeted)Tj T* 0.118 Tw (therapy in triple-negative breast cancer. Breast Cancer Res. Treat.)Tj 0 -1.42268 TD 0 Tw (134, 561-567. )Tj -1.65544 -1.42267 TD 0.049 Tw (Gucalp A. and Traina T.A. (2010). Triple-negative breast cancer: role of)Tj 1.65544 -1.42267 TD 0 Tw (the androgen receptor. Cancer J. 16, 62-65.)Tj -1.65544 -1.42266 TD 0.059 Tw (Guedj M., Marisa L., de Reynies A., Orsetti B., Schiappa R., Bibeau F.,)Tj 1.65544 -1.42266 TD 0.021 Tc 0.118 Tw (MacGrogan G., Lerebours F., Finetti P., Longy M., Bertheau P.,)Tj 0 -1.42267 TD 0 Tc 0.094 Tw (Bertrand F., Bonnet F., Martin A., Feugeas J., Bi\217che I., Lehmann-)Tj T* 0.04 Tc 0.099 Tw (Che J., Lidereau R., Birnbaum D., Bertucci F., de Th\216 H. and)Tj T* 0 Tc 0.136 Tw (Theillet C. (2012). A refined molecular taxonomy of breast cancer.)Tj 0 -1.42266 TD 0 Tw (Oncogene 31, 1196-1206. )Tj -1.65544 -1.42267 TD 0.138 Tw (Gupta D., Croitoru C., Ayala A., Sahin A. and Middleton L. (2002). E-)Tj 1.65544 -1.42267 TD 0.074 Tw (cadherin immunohistochemical analysis of histiocytoid carcinoma of)Tj 0 -1.42266 TD 0 Tw (the breast. Ann. Diagn. Pathol. 6, 141-147.)Tj -1.65544 -1.42266 TD 0.083 Tc 0.06 Tw (Gwin K., Lezon-Geyda K., Harris L. and Tavassoli F. (2011).)Tj 1.65544 -1.42267 TD 0.016 Tc 0.123 Tw (Chromosome 7 aneusomy in metaplastic breast carcinomas with)Tj T* 0.007 Tc 0.132 Tw (chondroid, squamous, and spindle-cell differentiation. Int. J. Surg.)Tj T* 0 Tc 0 Tw (Pathol. 19, 20-25. )Tj -1.65544 -1.42267 TD 0.065 Tw (Haagensen D., Dilley W., Mazoujian G. and Wells S. (1990). Review of)Tj 1.65544 -1.42267 TD 0.111 Tw (GCDFP-15. An apocrine marker protein. Ann. N.Y. Acad. Sci. 586,)Tj 0 -1.42266 TD 0 Tw (161-173. )Tj -1.65544 -1.42266 TD 0.077 Tw (Hasegawa M., Moritani S., Murakumo Y., Sato T., Hagiwara S., Suzuki)Tj 1.65544 -1.42267 TD 0.019 Tw (C., Mii S., Jijiwa M., Enomoto A., Asai N., Ichihara S. and Takahashi)Tj ET 0 0 0 0 k 45.354 729.071 504.567 14.1729 re f 45.354 715.927 504.567 12.002 re f 45.354 689.417 504.567 25.512 re f 45.354 729.071 504.567 14.1729 re f Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.7 0 0 7.7 46.3543 731.757 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (1404)Tj ET 0 0 0 0 k 45.354 715.927 504.567 12.002 re f Q /GS3 gs /GS2 gs q BT /F4 1 Tf 10.5 0 2.23185 10.5 220.6233 719.277 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Apocrine carcinoma of the breast)Tj ET Q endstream endobj 26 0 obj << /Length 12656 >> stream /GS0 gs /GS1 gs q /GS2 gs 0 0 0 0 k 45.354 44.774 242.363 644.153 re f Q /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 58.7701 682.461 Tm 0 Tr 0 0 0 1 k -0.0002 Tc (M)Tj 0.83282 0.00001 TD (.)Tj 0.57655 0 Td 0 Tc 0.021 Tw ((2008). CD109 expression in basal-like breast carcinoma. Pathol.)Tj -1.40937 -1.42267 TD 0 Tw (Int. 58, 288-294.)Tj -1.65544 -1.42266 TD 0.0082 Tc (H)Tj 0.7302 0.00001 TD 0.008 Tc 0.131 Tw (ickey T., Robinson J.L., Carroll J. and Tilley W. (2012). Minireview:)Tj 0.92524 -1.42268 TD 0.021 Tc 0.118 Tw (The androgen receptor in breast tissues: growth inhibitor, tumor)Tj 0 -1.42266 TD -0.0002 Tc (s)Tj 0.49981 0.00001 TD 0 Tc 0 Tw (uppressor, oncogene? Mol. Endocrinol. 26, 1252-1267. )Tj -2.15525 -1.42267 TD 0.01 Tc 0.129 Tw (Honma N., Sakamoto G., Akiyama F., Esaki Y., Sawabe M., Arai T.,)Tj 1.65544 -1.42267 TD 0.0299 Tc (H)Tj 0.7519 0.00001 TD 0.03 Tc 0.109 Tw (osoi T., Harada N., Younes M. and Takubo K. (2003). Breast)Tj -0.7519 -1.42267 TD -0.0002 Tc (c)Tj 0.49983 0.00001 TD 0 Tc 0.061 Tw (arcinoma in women over the age of 85: distinct histological pattern)Tj -0.49983 -1.42267 TD 0.055 Tc 0.083 Tw (and androgen, oestrogen, and progesterone receptor status.)Tj -0.0002 Tc (H)' 0.72181 0.00001 TD 0 Tc 0 Tw (istopathology 42, 120-127. )Tj -2.37725 -1.42267 TD 0.013 Tc 0.126 Tw (Honma N., Takubo K., Akiyama F., Sawabe M., Arai T., Younes M.,)Tj 1.65544 -1.42266 TD -0.0002 Tc (K)Tj 0.66684 0.00001 TD 0 Tc 0.099 Tw (asumi F. and Sakamoto G. (2005). Expression of GCDFP-15 and)Tj -0.66685 -1.42268 TD -0.0002 Tc (AR)Tj 1.72812 0 Td 0 Tc 0.062 Tw (decreases in larger or node-positive apocrine carcinomas of the)Tj -1.72812 -1.42266 TD -0.0002 Tc (b)Tj 0.55582 0.00001 TD 0 Tc 0 Tw (reast. Histopathology 47, 195-201. )Tj -2.21126 -1.42267 TD 0.087 Tw (Honma N., Takubo K., Arai T., Younes M., Kasumi F., Akiyama F. and)Tj 1.65544 -1.42267 TD 0.018 Tc 0.12 Tw (Sakamoto G. (2006). Comparative study of monoclonal antibody)Tj 0 -1.42266 TD 0.0418 Tc (B)Tj 0.70876 0.00001 TD 0.042 Tc 0.097 Tw (72.3 and gross cystic disease fluid protein-15 as markers of)Tj -0.70876 -1.42267 TD 0 Tc 0 Tw (apocrine carcinoma of the breast. APMIS 114, 712-719. )Tj -1.65544 -1.42266 TD 0.0187 Tc (H)Tj 0.74073 0.00001 TD 0.019 Tc 0.12 Tw (onma N., Takubo K., Akiyama F., Kasumi F., Sawabe M., Arai T.,)Tj 0.91471 -1.42268 TD 0.003 Tc 0.136 Tw (Hosoi T., Yoshimura N., Harada N., Younes M. and Sakamoto G.)Tj 0 -1.42267 TD 0.079 Tc 0.06 Tw ((2007). Expression of oestrogen receptor-beta in apocrine)Tj T* 0 Tc 0 Tw (carcinomas of the breast. Histopathology 50, 425-433. )Tj -1.65544 -1.42267 TD 0.11 Tw (Honma N., Saji S., Kurabayashi R., Aida J., Arai T., Horii R., Akiyama)Tj 1.65544 -1.42267 TD 0.062 Tc 0.077 Tw (F., Iwase T., Harada N., Younes M., Toi M., Takubo K. and)Tj T* 0.006 Tc 0.132 Tw (Sakamoto G. (2008). Oestrogen receptor-beta1 but not oestrogen)Tj T* 0 Tc 0.105 Tw (receptor-betacx is of prognostic value in apocrine carcinoma of the)Tj T* 0 Tw (breast. APMIS 116, 923-930. )Tj -1.65544 -1.42267 TD 0.033 Tw (Hu R., Dawood S., Holmes M., Collins L., Schnitt S., Cole K., Marotti J.,)Tj 1.65544 -1.42267 TD 0.08 Tw (Hankinson S., Colditz G. and Tamimi R. (2011). Androgen receptor)Tj T* 0.003 Tc 0.135 Tw (expression and breast cancer survival in postmenopausal women.)Tj T* 0 Tc 0 Tw (Clin. Cancer Res. 17, 1867-1874. )Tj -1.65544 -1.42267 TD 0.002 Tc 0.137 Tw (Iggo R. (2011). New insights into the role of androgen and oestrogen)Tj 1.65544 -1.42267 TD 0 Tc 0.028 Tw (receptors in molecular apocrine breast tumours. Breast Cancer Res.)Tj T* 0 Tw (13, 318. )Tj -1.65544 -1.42266 TD 0.101 Tw (Iizuka M., Enomoto K. and Sakurai K. (2012). A case of breast cancer)Tj 1.65544 -1.42267 TD 0.001 Tc 0.138 Tw (treated with neoadjuvant chemotherapy and segmentectomy. Gan.)Tj 0 -1.42266 TD 0 Tc 0 Tw (To. Kagaku. Ryoho. 39, 2027-2029. )Tj -1.65544 -1.42267 TD 0.044 Tc 0.095 Tw (Isola J. (1993). Immunohistochemical demonstration of androgen)Tj 1.65544 -1.42267 TD 0.016 Tc 0.123 Tw (receptor in breast cancer and its relationship to other prognostic)Tj 0 -1.42268 TD 0 Tc 0 Tw (factors. J. Pathol. 170, 31-35. )Tj -1.65544 -1.42267 TD 0.001 Tc 0.138 Tw (Iwase H., Kurebayashi J., Tsuda H., Ohta T., Kurosumi M., Miyamoto)Tj 1.65544 -1.42267 TD 0 Tc 0.069 Tw (K., Yamamoto Y. and Iwase T. (2010). Clinicopathological analyses)Tj 0 -1.42266 TD 0.019 Tc 0.119 Tw (of triple negative breast cancer using surveillance data from the)Tj T* 0.02 Tc 0.118 Tw (Registration Committee of the Japanese Breast Cancer Society.)Tj 0 -1.42267 TD 0 Tc 0 Tw (Breast Cancer 17, 118-124.)Tj -1.65544 -1.42267 TD 0.124 Tw (Jang K.S., Han H.X., Paik S.S., Brown P.H. and Kong G. (2006). Id-1)Tj 1.65544 -1.42267 TD 0.019 Tc 0.119 Tw (overexpression in invasive ductal carcinoma cells is significantly)Tj 0 -1.42266 TD 0.083 Tc 0.241 Tw (associated with intratumoral microvessel density in ER-)Tj 0 -1.42267 TD 0 Tc 0 Tw (negative/node-positive breast cancer. Cancer Lett. 244, 203-210.)Tj -1.65544 -1.42267 TD 0.1 Tw (Japaze H., Emina J., Diaz C., Schwam R., Gercovich N., Demonty G.,)Tj 1.65544 -1.42266 TD 0.007 Tc 0.132 Tw (Morgenfeld E., Rivarola E., Gil Deza E. and Gercovich F. (2005).)Tj T* 0.083 Tc 0.173 Tw (\324Pure\325 invasive apocrine carcinoma of the breast: a new)Tj 0 -1.42267 TD 0 Tc 0 Tw (clinicopathological entity? Breast 14, 3-10. )Tj -1.6554 -1.4227 TD 0.078 Tw (Jones C., Damiani S., Wells D., Chaggar R., Lakhani S. and Eusebi V.)Tj 1.6554 -1.4227 TD 0.007 Tc 0.132 Tw ((2001). Molecular cytogenetic comparison of apocrine hyperplasia)Tj T* 0 Tc 0 Tw (and apocrine carcinoma of the breast. Am. J. Pathol. 158, 207-214. )Tj -1.6554 -1.4227 TD 0.06 Tw (Karameris A., Worthy E., Gorgoulis V., Quezado M. and Anastassiades)Tj 1.6554 -1.4227 TD 0.011 Tw (O. (1995). p53 gene alterations in special types of breast carcinoma:)Tj -0.0002 Tc (a)' 0.9311 0 Td 0 Tc 0.098 Tw (molecular and immunohistochemical study in archival material. J.)Tj -0.9311 -1.4227 TD 0 Tw (Pathol. 176, 361-372. )Tj ET 0 0 0 0 k 307.559 44.149 242.362 644.778 re f BT /F3 1 Tf 7.5 0 0 7.5 308.559 682.461 Tm 0 0 0 1 k -0.0001 Tc (K)Tj 0.66685 0.00001 TD 0 Tc 0.13 Tw (asami M., Gobbi H., Dupont W., Simpson J., Page D. and Vnencak-)Tj 0.98859 -1.42267 TD 0.002 Tc 0.136 Tw (Jones C. (2000). Androgen receptor CAG repeat lengths in ductal)Tj 0 -1.42266 TD -0.0002 Tc (c)Tj 0.49979 0.00001 TD 0 Tc 0 Tw (arcinoma )Tj ET Q /GS3 gs /GS2 gs q BT /F4 1 Tf 7.5 0 1.59418 7.5 357.8305 661.121 Tm 0 Tr 0 0 0 1 k -0.0002 Tc (i)Tj 0.22182 0.00001 TD (n)Tj 0.85882 0 Td 0 Tc 0 Tw (situ)Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 379.8768 661.121 Tm 0 Tr 0 0 0 1 k -0.0002 Tc (o)Tj 0.55585 0.00001 TD (f)Tj 0.58086 0 Td 0 Tc 0.025 Tw (breast, longest in apocrine variety. Breast 9, 23-)Tj -8.99031 -1.42268 TD 0 Tw (27. )Tj -1.65544 -1.42266 TD 0.0324 Tc (K)Tj 0.69936 0.00001 TD 0.032 Tc 0.106 Tw (asashima S., Kawashima A., Ozaki S. and Nakanuma Y. (2012).)Tj 0.95608 -1.42267 TD 0 Tc 0.074 Tw (Expression of 5\341-reductase in apocrine carcinoma of the breast and)Tj 0.0832 Tc (i)' 0.30521 0.00001 TD 0.083 Tc 0.479 Tw (ts correlation with clinicopathological aggressiveness.)Tj -0.30521 -1.42267 TD -0.0002 Tc (H)Tj 0.72183 0.00001 TD 0 Tc 0 Tw (istopathology 60, E51-E57. )Tj -2.37727 -1.42267 TD 0.039 Tc 0.1 Tw (Kaya H., Bozkurt S., Erbarut I. and Djamgoz M. (2008). Apocrine)Tj 1.65544 -1.42267 TD -0.0002 Tc (c)Tj 0.49983 0.00001 TD 0 Tc 0.111 Tw (arcinomas of the breast in Turkish women: hormone receptors, c-)Tj -0.49983 -1.42267 TD 0.006 Tc 0.133 Tw (erbB-2 and p53 immunoexpression. Pathol. Res. Pract. 204, 367-)Tj 0 -1.42266 TD -0.0002 Tc (3)Tj 0.5558 0.00001 TD 0 Tc 0 Tw (71. )Tj -2.21124 -1.42268 TD 0.005 Tc 0.134 Tw (Kim S., Jung W. and Koo J. (2012). Differences in autophagy-related)Tj 1.65544 -1.42266 TD 0.0438 Tc (a)Tj 0.59978 0.00001 TD 0.044 Tc 0.095 Tw (ctivity by molecular subtype in triple-negative breast cancer.)Tj -0.59978 -1.42267 TD 0 Tc 0 Tw (Tumour Biol. 33, 1681-1694. )Tj -1.65544 -1.42267 TD 0.083 Tc 0.065 Tw (Koletsa T., Kotoula V., Karayannopoulou G., Nenopoulou E.,)Tj 1.65544 -1.42266 TD -0.0002 Tc (K)Tj 0.66684 0.00001 TD 0 Tc 0.139 Tw (arkavelas G., Papadimitriou C. and Kostopoulos I. (2010). EGFR)Tj -0.66684 -1.42267 TD 0.099 Tw (expression and activation are common in HER2 positive and triple-)Tj 0 -1.42266 TD -0.0002 Tc (n)Tj 0.55583 0.00001 TD 0 Tc 0 Tw (egative breast tumours. Histol. Histopathol. 25, 1171-1179. )Tj -2.21127 -1.42268 TD 0.032 Tw (Konecny G. (2012). Emerging strategies for the dual inhibition of HER2-)Tj 1.65544 -1.42267 TD 0 Tw (positive breast cancer. Curr. Opin. Obstet. Gynecol. 25, 55-65.)Tj -1.65544 -1.42267 TD 0.015 Tc 0.124 Tw (Kreike B., van Kouwenhove M., Horlings H., Weigelt B., Peterse H.,)Tj 1.65544 -1.42267 TD 0 Tc 0.078 Tw (Bartelink H. and van de Vijver M. (2007). Gene expression profiling)Tj T* 0.015 Tc 0.124 Tw (and histopathological characterization of triple-negative/basal-like)Tj T* 0 Tc 0 Tw (breast carcinomas. Breast Cancer Res. 9, R65. )Tj -1.65544 -1.42267 TD 0.012 Tc 0.127 Tw (Laforga J., Gasent J. and S\207nchez I. (2011). Encapsulated apocrine)Tj 1.65544 -1.42267 TD 0 Tc 0.09 Tw (papillary carcinoma of the breast: case report with clinicopathologic)Tj T* 0 Tw (and immunohistochemical study. Diagn. Cytopathol. 39, 288-293. )Tj -1.65544 -1.42267 TD 0.002 Tc 0.137 Tw (Lakhani S.R., Ellis I.O., Schnitt S.J., Tan P.H. and van de Vijver M.J.)Tj 1.65544 -1.42267 TD 0 Tc 0 Tw ((2012). WHO classification of tumours of the breast. IARC. Lyon.)Tj -1.65544 -1.42267 TD 0.033 Tc 0.106 Tw (Lambot M.A., Eddafali B., Simon P., Fayt I. and No\221l J.C. (2001).)Tj 1.65544 -1.42267 TD 0 Tc 0.056 Tw (Metastasis from apocrine carcinoma of the breast to an endometrial)Tj T* 0 Tw (polyp. Virchows Arch. 438, 517-518.)Tj -1.65544 -1.42267 TD 0.001 Tc 0.138 Tw (Leal C., Henrique R., Monteiro P., Lopes C., Bento M., De Sousa C.,)Tj 1.65544 -1.42266 TD 0 Tc 0.136 Tw (Lopes P., Olson S., Silva M. and Page D. (2001). Apocrine ductal)Tj 0 -1.42267 TD 0.063 Tc 0.076 Tw (carcinoma in situ of the breast: histologic classification and)Tj 0 -1.42266 TD 0 Tc 0 Tw (expression of biologic markers. Hum. Pathol. 32, 487-493. )Tj -1.65544 -1.42267 TD 0.054 Tw (Lehmann B.D., Bauer J.A., Chen Xi., Sanders M.E., Chakravarthy A.B.,)Tj 1.65544 -1.42267 TD 0.016 Tc 0.123 Tw (Shyr Y. and Pietenpol J.A. (2011). Identification of human triple-)Tj 0 -1.42268 TD 0 Tc 0.021 Tw (negative breast cancer subtypes and preclinical models for selection)Tj 0 -1.42267 TD 0 Tw (of targeted therapies. J. Clin. Invest. 121, 2750-2767.)Tj -1.65544 -1.42267 TD 0.023 Tc 0.116 Tw (Lewis G., Subhawong A., Nassar H., Vang R., Illei P., Park B. and)Tj 1.65544 -1.42266 TD 0.049 Tc 0.089 Tw (Argani P. (2011). Relationship between molecular subtype of)Tj T* 0.006 Tc 0.133 Tw (invasive breast carcinoma and expression of gross cystic disease)Tj 0 -1.42267 TD 0.007 Tc 0.132 Tw (fluid protein 15 and mammaglobin. Am. J. Clin. Pathol. 135, 587-)Tj T* 0 Tc 0 Tw (591. )Tj -1.65544 -1.42267 TD 0.028 Tc 0.11 Tw (Liegl B., Horn L.C. and Moinfar F. (2005). Androgen receptors are)Tj 1.65544 -1.42266 TD 0.041 Tc 0.098 Tw (frequently expressed in mammary and extramammary Paget\325s)Tj 0 -1.42267 TD 0 Tc 0 Tw (disease. Mod. Pathol. 18, 1283-1288. )Tj -1.65544 -1.42267 TD 0.061 Tc 0.078 Tw (Lininger R., Zhuang Z., Man Y., Park W., Emmert-Buck M. and)Tj 1.65544 -1.42266 TD 0.081 Tc 0.057 Tw (Tavassoli F. (1999). Loss of heterozygosity is detected at)Tj T* 0 Tc 0.032 Tw (chromosomes 1p35-36 (NB), 3p25 (VHL), 16p13 (TSC2/PKD1), and)Tj 0 -1.42267 TD 0.083 Tw (17p13 (TP53) in microdissected apocrine carcinomas of the breast.)Tj T* 0 Tw (Mod. Pathol. 12, 1083-1089. )Tj -1.65544 -1.42267 TD 0.013 Tc 0.126 Tw (Lobaccaro J., Lumbroso S., Belon C., Galtier-Dereure F., Bringer J.,)Tj 1.65544 -1.42267 TD 0.011 Tc 0.128 Tw (Lesimple T., Namer M., Cutuli B., Pujol H. and Sultan C. (1993).)Tj T* 0 Tc 0.062 Tw (Androgen receptor gene mutation in male breast cancer. Hum. Mol.)Tj 0 -1.42266 TD 0 Tw (Genet. 2, 1799-1802. )Tj -1.65544 -1.42266 TD 0.036 Tw (Lu Y., Zi X., Zhao Y., Mascarenhas D. and Pollak M. (2001). Insulin-like)Tj 1.65544 -1.42267 TD 0.021 Tc 0.118 Tw (growth factor-I receptor signaling and resistance to trastuzumab)Tj ET 0 0 0 0 k 45.354 729.071 504.567 14.1729 re f Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.7 0 0 7.7 531.7993 731.757 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (1405)Tj ET 0 0 0 0 k 45.354 716.262 504.567 12 re f Q /GS3 gs /GS2 gs q BT /F4 1 Tf 10.5 0 2.23185 10.5 220.6233 719.6104 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Apocrine carcinoma of the breast)Tj ET 0 0 0 0 k 45.354 689.417 504.567 25.512 re f Q endstream endobj 27 0 obj << /Length 12002 >> stream /GS0 gs /GS1 gs q /GS2 gs 0 0 0 0 k 45.354 51.023 242.363 637.904 re f Q /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 58.7701 682.461 Tm 0 Tr 0 0 0 1 k -0.0002 Tc (\()Tj 0.33284 0.00001 TD 0 Tc 0 Tw (Herceptin\). J. Natl. Cancer. Inst. 93, 1852-1857. )Tj -1.98828 -1.42267 TD 0.08 Tw (Mardi K., Sharma J. and Sharma N. (2004). Apocrine carcinoma of the)Tj 1.65544 -1.42266 TD -0.0002 Tc (b)Tj 0.55584 0.00001 TD 0 Tc 0.014 Tw (reast presenting as a solitary cyst: cytological and histopathological)Tj -0.55584 -1.42268 TD 0 Tw (study of a case. Indian J. Pathol. Microbiol. 47, 268-270.)Tj -1.65544 -1.42266 TD -0.0001 Tc (M)Tj 0.83286 0.00001 TD 0 Tc 0.07 Tw (artin V., Botta F., Zanellato E., Molinari F., Crippa S., Mazzucchelli L.)Tj 0.82258 -1.42267 TD 0.026 Tc 0.113 Tw (and Frattini M. (2012). Molecular characterization of EGFR and)Tj 0.0091 Tc (E)' 0.6761 0.00001 TD 0.009 Tc 0.13 Tw (GFR-downstream pathways in triple negative breast carcinomas)Tj -0.6761 -1.42267 TD -0.0002 Tc (w)Tj 0.72183 0.00001 TD 0 Tc 0 Tw (ith basal like features. Histol. Histopathol. 27, 785-792. )Tj -2.37727 -1.42267 TD 0.033 Tc 0.106 Tw (Maruyama N., Miyoshi Y., Taguchi T., Tamaki Y., Monden M. and)Tj 1.65544 -1.42267 TD -0.0002 Tc (N)Tj 0.72183 0.00001 TD 0 Tc 0.042 Tw (oguchi S. (2007). Clinicopathologic analysis of breast cancers with)Tj -0.72183 -1.42266 TD 0.08 Tw (PIK3CA mutations in Japanese women. Clin. Cancer Res. 13, 408-)Tj 0 -1.42267 TD -0.0002 Tc (4)Tj 0.5558 0.00001 TD 0 Tc 0 Tw (14. )Tj -2.21124 -1.42267 TD 0.01 Tw (Masood S. and Rosa M. (2009). The challenge of apocrine proliferations)Tj 1.65544 -1.42267 TD -0.0002 Tc (o)Tj 0.55584 0.00001 TD (f)Tj 0.57197 0 Td 0 Tc 0.016 Tw (the breast: a morphologic approach. Pathol. Res. Pract. 205, 155-)Tj -1.1278 -1.42266 TD 0 Tw (164. )Tj -1.65544 -1.42267 TD 0.004 Tw (Masuda H., Zhang D., Bartholomeusz C., Doihara H., Hortobagyi G. and)Tj 1.65544 -1.42267 TD -0.0002 Tc (U)Tj 0.72181 0.00001 TD 0 Tc 0.106 Tw (eno N. (2012). Role of epidermal growth factor receptor in breast)Tj -0.72182 -1.42267 TD 0 Tw (cancer. Breast Cancer Res. Treat. 136, 331-345.)Tj -1.65544 -1.42266 TD 0.0574 Tc (M)Tj 0.89039 0.00001 TD 0.057 Tc 0.081 Tw (atsubara N., Mukai H., Fujii S. and Wada N. (2013). Different)Tj 0.76505 -1.42268 TD 0.025 Tc 0.114 Tw (prognostic significance of Ki-67 change between pre- and post-)Tj 0 -1.42267 TD 0.015 Tc 0.124 Tw (neoadjuvant chemotherapy in various subtypes of breast cancer.)Tj T* 0 Tc 0 Tw (Breast Cancer Res. Treat. 137, 203-212. )Tj -1.65544 -1.42267 TD 0.07 Tc 0.069 Tw (Matsuo K., Fukutomi T., Tsuda H., Kanai Y., Tanaka S.A. and)Tj 1.65544 -1.42267 TD 0.083 Tc 0.214 Tw (Nanasawa T. (1998). Apocrine carcinoma of the breast:)Tj T* 0.002 Tc 0.137 Tw (Clinicopathological analysis and histological subclassification of 12)Tj T* 0 Tc 0 Tw (cases. Breast Cancer 5, 279-284. )Tj -1.65544 -1.42267 TD 0.042 Tw (Matsuo K., Fukutomi T., Hasegawa T., Akashi-Tanaka S., Nanasawa T.)Tj 1.65544 -1.42267 TD 0.058 Tc 0.081 Tw (and Tsuda H. (2002). Histological and immunohistochemical)Tj T* 0 Tc 0 Tw (analysis of apocrine breast carcinoma. Breast Cancer 9, 43-49. )Tj -1.65544 -1.42267 TD 0.018 Tc 0.121 Tw (Mazoujian G., Bodian C., Haagensen D. and Haagensen C. (1989).)Tj 1.65544 -1.42267 TD 0.028 Tc 0.111 Tw (Expression of GCDFP-15 in breast carcinomas. Relationship to)Tj T* 0 Tc 0 Tw (pathologic and clinical factors. Cancer 63, 2156-2161.)Tj -1.65544 -1.42267 TD 0.139 Tw (McGhan L.J., McCullough A.E., Protheroe C.A., Dueck A.C., Lee J.J.,)Tj 1.65544 -1.42267 TD 0.005 Tw (Nunez R., Castle E.P., Gray R.J., Wasif N., Goetz M.P., Hawse J.R.,)Tj 0 -1.42266 TD 0.029 Tc 0.11 Tw (Henry T.J., Barrett M.T., Heather C.E. and Pockaj B.A. (2012).)Tj 0 -1.42267 TD 0.001 Tc 0.138 Tw (Androgen receptor-positive triple negative breast cancer: A unique)Tj 0 -1.42266 TD 0.056 Tc 0.082 Tw (breast cancer subtype. Ann. Surg. Oncol. 19 (suppl.1), S12.)Tj 0 -1.42267 TD 0 Tc 0 Tw ((Abstract))Tj -1.65544 -1.42267 TD 0.073 Tw (Micello D., Marando A., Sahnane N., Riva C., Capella C. and Sessa F.)Tj 1.65544 -1.42268 TD 0.016 Tw ((2010). Androgen receptor is frequently expressed in HER2-positive,)Tj 0 -1.42267 TD 0 Tw (ER/PR-negative breast cancers. 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Cancer 98, 703-711. )Tj -1.65544 -1.42267 TD 0.038 Tc 0.101 Tw (Monhollen L., Morrison C., Ademuyiwa F., Chandrasekhar R. and)Tj 1.6554 -1.4227 TD 0.034 Tc 0.104 Tw (Khoury T. (2012). Pleomorphic lobular carcinoma: a distinctive)Tj T* 0.002 Tc 0.137 Tw (clinical and molecular breast cancer type. Histopathology 61, 365-)Tj T* 0 Tc 0 Tw (377. )Tj -1.6554 -1.4227 TD 0.005 Tc 0.134 Tw (Montagna E., Maisonneuve P., Rotmensz N., Cancello G., Iorfida M.,)Tj 1.6554 -1.4227 TD 0.054 Tc 0.085 Tw (Balduzzi A., Galimberti V., Veronesi P., Luini A., Pruneri G.,)Tj T* 0 Tc 0.043 Tw (Bottiglieri L., Mastropasqua M., Goldhirsch A., Viale G. and Colleoni)Tj ET 0 0 0 0 k 307.559 51.023 242.362 637.904 re f BT /F3 1 Tf 7.5 0 0 7.5 320.9748 682.461 Tm 0 0 0 1 k -0.0002 Tc (M)Tj 0.83282 0.00001 TD (.)Tj 0.64291 0 Td 0 Tc 0.087 Tw ((2013). Heterogeneity of triple-negative breast cancer: histologic)Tj -1.47573 -1.42267 TD 0 Tw (subtyping to inform the outcome. Clin. Breast Cancer 13, 31-39. )Tj -1.65544 -1.42266 TD 0.0016 Tc (M)Tj 0.83459 0.00001 TD 0.002 Tc 0.137 Tw (oore N., Buchanan G., Harris J., Selth L., Bianco-Miotto T., Hanson)Tj 0.82085 -1.42268 TD 0 Tc 0.051 Tw (A., Birrell S., Butler L., Hickey T. and Tilley W. (2012). An androgen)Tj 0 -1.42266 TD -0.0002 Tc (r)Tj 0.33281 0.00001 TD 0 Tc 0.136 Tw (eceptor mutation in the MDA-MB-453 cell line model of molecular)Tj -0.33281 -1.42267 TD 0.035 Tc 0.104 Tw (apocrine breast cancer compromises receptor activity. Endocr.)Tj -0.0002 Tc (R)' 0.72181 0.00001 TD 0 Tc 0 Tw (elat. Cancer 19, 599-613. )Tj -2.37725 -1.42267 TD -0.0001 Tc (M)Tj 0.83285 0.00001 TD 0 Tc 0.085 Tw (oritani S., Ichihara S., Hasegawa M., Endo T., Oiwa M., Shiraiwa M.,)Tj 0.82259 -1.42267 TD 0.033 Tc 0.106 Tw (Nishida C., Morita T., Sato Y., Hayashi T. and Kato A. (2011).)Tj 0.0202 Tc (I)' 0.29817 0.00001 TD 0.02 Tc 0.119 Tw (ntracytoplasmic lipid accumulation in apocrine carcinoma of the)Tj -0.29817 -1.42267 TD 0.005 Tc 0.134 Tw (breast evaluated with adipophilin immunoreactivity: a possible link)Tj 0 -1.42266 TD -0.0002 Tc (b)Tj 0.55582 0.00001 TD 0 Tc 0.09 Tw (etween apocrine carcinoma and lipid-rich carcinoma. Am. J. Surg.)Tj -0.55582 -1.42268 TD 0 Tw (Pathol. 35, 861-867. )Tj -1.65544 -1.42266 TD -0.0001 Tc (M)Tj 0.83285 0.00001 TD 0 Tc 0.087 Tw (oriya T., Sakamoto K., Sasano H., Kawanaka M., Sonoo H., Manabe)Tj 0.82259 -1.42267 TD 0.006 Tc 0.132 Tw (T. and Ito J. (2000). Immunohistochemical analysis of Ki-67, p53,)Tj T* 0 Tc 0.004 Tw (p21, and p27 in benign and malignant apocrine lesions of the breast:)Tj 0 -1.42266 TD -0.0002 Tc (i)Tj 0.22184 0.00001 TD 0 Tc 0.025 Tw (ts correlation to histologic findings in 43 cases. Mod. Pathol. 13, 13-)Tj -0.22184 -1.42267 TD 0 Tw (18. )Tj -1.65544 -1.42266 TD -0.0001 Tc (M)Tj 0.83287 0.00001 TD 0 Tc 0.029 Tw (ossler J., Barton T., Brinkhous A., McCarty K., Moylan J. and McCarty)Tj 0.82257 -1.42268 TD 0.004 Tc 0.134 Tw (K. (1980). Apocrine differentiation in human mammary carcinoma.)Tj 0 -1.42267 TD 0 Tc 0 Tw (Cancer 46, 2463-2471. )Tj -1.65544 -1.42267 TD 0.036 Tw (Naderi A. and Hughes-Davies L. (2008). A functionally significant cross-)Tj 1.65544 -1.42267 TD 0.009 Tc 0.129 Tw (talk between androgen receptor and ErbB2 pathways in estrogen)Tj T* 0 Tc 0 Tw (receptor negative breast cancer. Neoplasia 10, 542-548. )Tj -1.65544 -1.42267 TD 0.019 Tw (Naderi A. and Liu J. (2010). Inhibition of androgen receptor and Cdc25A)Tj 1.65544 -1.42267 TD 0.053 Tc 0.086 Tw (phosphatase as a combination targeted therapy in molecular)Tj T* 0 Tc 0 Tw (apocrine breast cancer. Cancer Lett. 298, 74-87. )Tj -1.65544 -1.42267 TD 0.019 Tc 0.119 Tw (Naderi A., Chia K. and Liu J. (2011). Synergy between inhibitors of)Tj 1.65544 -1.42267 TD 0.065 Tc 0.074 Tw (androgen receptor and MEK has therapeutic implications in)Tj T* 0.003 Tc 0.135 Tw (estrogen receptor-negative breast cancer. Breast Cancer Res. 13,)Tj T* 0 Tc 0 Tw (R36. )Tj -1.65544 -1.42267 TD 0.067 Tw (Naderi A. and Meyer M. (2012). Prolactin-induced protein mediates cell)Tj 1.65544 -1.42267 TD 0.039 Tc 0.1 Tw (invasion and regulates integrin signaling in estrogen receptor-)Tj T* 0 Tc 0 Tw (negative breast cancer. Breast Cancer Res. 14, R111.)Tj -1.65544 -1.42266 TD 0.106 Tw (Nagao T., Kinoshita T., Hojo T., Tsuda H., Tamura K. and Fujiwara Y.)Tj 1.65544 -1.42267 TD 0.005 Tw ((2012). The differences in the histological types of breast cancer and)Tj 0 -1.42266 TD 0.059 Tc 0.08 Tw (the response to neoadjuvant chemotherapy: the relationship)Tj 0 -1.42267 TD 0.018 Tc 0.12 Tw (between the outcome and the clinicopathological characteristics.)Tj T* 0 Tc 0 Tw (Breast 21, 289-295. )Tj -1.65544 -1.42268 TD 0.069 Tw (Narita D., Anghel A., Cimpean A., Izvernariu D., Cireap N., Ilina R. and)Tj 1.65544 -1.42267 TD 0.022 Tc 0.116 Tw (Ursoniu S. (2010). Interaction between estrogens and androgen)Tj T* 0.056 Tc 0.083 Tw (receptor genes microsatellites, prostate-specific antigen and)Tj 0 -1.42266 TD 0 Tc 0.027 Tw (androgen receptor expressions in breast cancer. Neoplasm 57, 198-)Tj T* 0 Tw (206. )Tj -1.65544 -1.42267 TD 0.029 Tw (Ni M., Chen Y., Lim E., Wimberly H., Bailey S., Imai Y., Rimm D., Liu X.)Tj 1.65544 -1.42267 TD 0.029 Tc 0.11 Tw (and Brown M. (2011). Targeting androgen receptor in estrogen)Tj T* 0 Tc 0 Tw (receptor-negative breast cancer. 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Pathol. 11, 1-9. )Tj -1.65544 -1.42266 TD 0.105 Tw (O\325Malley F. and Bane A. (2008). An update on apocrine lesions of the)Tj 1.65544 -1.42266 TD 0 Tw (breast. Histopathology. 52, 3-10. )Tj ET 0 0 0 0 k 45.354 729.071 504.567 14.1729 re f Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.7 0 0 7.7 46.3543 731.757 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (1406)Tj ET 0 0 0 0 k 45.354 715.927 504.567 12.002 re f Q /GS3 gs /GS2 gs q BT /F4 1 Tf 10.5 0 2.23185 10.5 220.6233 719.277 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Apocrine carcinoma of the breast)Tj ET 0 0 0 0 k 45.354 689.417 504.567 25.512 re f Q endstream endobj 28 0 obj << /Length 11953 >> stream /GS0 gs /GS1 gs q /GS2 gs 0 0 0 0 k 45.354 51.023 242.363 637.904 re f Q /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 46.3543 682.461 Tm 0 Tr 0 0 0 1 k -0.0002 Tc (O)Tj 0.77785 0.00001 TD 0 Tc 0.085 Tw (\325Malley F.P., Pinder S.E. and Muligan A.M. (2011). Breast Pathology.)Tj 0.87759 -1.42267 TD 0 Tw (2nd edition. Saunders Elsevier.)Tj -1.65544 -1.42266 TD -0.0001 Tc (P)Tj 0.66686 0.00001 TD 0 Tc 0.105 Tw (agani A., Sapino A., Eusebi V., Bergnolo P. and Bussolati G. (1994).)Tj 0.98858 -1.42268 TD 0.032 Tc 0.106 Tw (PIP/GCDFP-15 gene expression and apocrine differentiation in)Tj 0 -1.42266 TD -0.0002 Tc (c)Tj 0.49984 0.00001 TD 0 Tc 0 Tw (arcinomas of the breast. Virchows Arch. 425, 459-465. )Tj -2.15528 -1.42267 TD (Page D.L. (2005). Apocrine carcinomas of the breast. Breast 14, 1-2.)Tj -0.0001 Tc (P)' 0.66687 0.00001 TD 0 Tc 0.121 Tw (alacios J., Sarri\227 D., Garc\222a-Macias M.C., Bryant B., Sobel M.E. and)Tj 0.98857 -1.42267 TD -0.0002 Tc (M)Tj 0.83283 0.00001 TD 0 Tc 0.006 Tw (erino M.J. (2003). Frequent E-cadherin gene inactivation by loss of)Tj -0.83283 -1.42267 TD 0.049 Tw (heterozygosity in pleomorphic lobular carcinoma of the breast. Mod.)Tj -0.0002 Tc (P)' 0.66682 0.00001 TD 0 Tc 0 Tw (athol. 16, 674-678.)Tj -2.32225 -1.42267 TD 0.018 Tw (Paredes J., Correia A.L., Ribeiro A.S., Milanezi F., Cameselle-Teijeiro J.)Tj 1.65544 -1.42266 TD -0.0002 Tc (a)Tj 0.55585 0.00001 TD 0 Tc 0.068 Tw (nd Schmitt F.C. (2008). Breast carcinomas that co-express E- and)Tj -0.55585 -1.42268 TD 0.083 Tc 0.133 Tw (P-cadherin are associated with p120-catenin cytoplasmic)Tj 0 -1.42266 TD -0.0002 Tc (l)Tj 0.22183 0.00001 TD 0 Tc 0 Tw (ocalisation and poor patient survival. J. Clin. Pathol. 61, 856-862.)Tj -1.87727 -1.42267 TD 0.002 Tw (Park S., Koo J., Kim M., Park H., Lee J., Lee J., Kim S., Park B. and Lee)Tj 1.65544 -1.42267 TD 0.119 Tw (K. (2011). Androgen receptor expression is significantly associated)Tj 0 -1.42266 TD 0.0032 Tc (w)Tj 0.72518 0.00001 TD 0.003 Tc 0.136 Tw (ith better outcomes in estrogen receptor-positive breast cancers.)Tj -0.72518 -1.42267 TD 0 Tc 0 Tw (Ann. Oncol. 22, 1755-1762. )Tj -1.65544 -1.42266 TD 0.0254 Tc (P)Tj 0.69237 0.00001 TD 0.025 Tc 0.113 Tw (erou C., S\277rlie T., Eisen M., van de Rijn M., Jeffrey S., Rees C.,)Tj 0.96307 -1.42268 TD 0.083 Tc 0.302 Tw (Pollack J., Ross D., Johnsen H., Akslen L., Fluge O.,)Tj 0 -1.42267 TD 0.012 Tc 0.126 Tw (Pergamenschikov A., Williams C., Zhu S., L\277nning P., B\277rresen-)Tj T* 0.018 Tc 0.121 Tw (Dale A., Brown P. and Botstein D. (2000). Molecular portraits of)Tj T* 0 Tc 0 Tw (human breast tumours. Nature 406, 747-752. )Tj -1.65544 -1.42267 TD 0.005 Tc 0.134 Tw (Phuah S.Y., Looi L.M., Hassan N., Rhodes A., Dean S., Taib N., Yip)Tj 1.65544 -1.42267 TD 0 Tc 0.074 Tw (C.H. and Teo S.H. (2012). Triple-negative breast cancer and PTEN)Tj T* 0.09 Tw ((phosphatase and tensin homologue) loss are predictors of BRCA1)Tj T* 0.011 Tc 0.128 Tw (germline mutations in women with early-onset and familial breast)Tj T* 0.017 Tc 0.122 Tw (cancer, but not in women with isolated late-onset breast cancer.)Tj T* 0 Tc 0 Tw (Breast Cancer Res. 14, R142.)Tj -1.65544 -1.42267 TD 0.059 Tw (Rakha E., Putti T., Abd El-Rehim D., Paish C., Green A., Powe D., Lee)Tj 1.65544 -1.42267 TD 0.083 Tc 0.243 Tw (A., Robertson J. and Ellis I. (2006). Morphological and)Tj T* 0.017 Tc 0.122 Tw (immunophenotypic analysis of breast carcinomas with basal and)Tj T* 0 Tc 0 Tw (myoepithelial differentiation. J. Pathol. 208, 495-506. )Tj -1.65544 -1.42267 TD 0.022 Tc 0.117 Tw (Rakha E., El-Sayed M., Green A., Lee A., Robertson J. and Ellis I.)Tj 1.65544 -1.42266 TD 0 Tc 0.088 Tw ((2007). Prognostic markers in triple-negative breast cancer. Cancer)Tj 0 -1.42267 TD 0 Tw (109, 25-32. )Tj -1.65544 -1.42266 TD 0.104 Tw (Reis-Filho J.S., Simpson P.T., Jones C., Steele D., Mackay A., Iravani)Tj 1.65544 -1.42267 TD 0.074 Tw (M., Fenwick K., Valgeirsson H., Lambros M., Ashworth A., Palacios)Tj T* 0.059 Tc 0.08 Tw (J., Schmitt F. and Lakhani S.R. (2005). Pleomorphic lobular)Tj 0 -1.42268 TD 0 Tc 0.042 Tw (carcinoma of the breast: role of comprehensive molecular pathology)Tj 0 -1.42267 TD 0 Tw (in characterization of an entity. J. Pathol. 207, 1-13.)Tj -1.65544 -1.42267 TD 0.1 Tw (Robinson J.L., Macarthur S., Ross-Innes C., Tilley W., Neal D., Mills I.)Tj 1.65544 -1.42266 TD 0.028 Tc 0.111 Tw (and Carroll J. (2011). Androgen receptor driven transcription in)Tj T* 0 Tc 0.13 Tw (molecular apocrine breast cancer is mediated by FoxA1. EMBO J.)Tj 0 -1.42267 TD 0 Tw (30, 3019-3027. )Tj -1.65544 -1.42267 TD 0.098 Tw (Roddy H. and Silverberg S. (1980). Ultrastructural analysis of apocrine)Tj 1.65544 -1.42267 TD 0 Tw (carcinoma of the human breast. Ultrastruct. Pathol. 1, 385-393. )Tj -1.65544 -1.42266 TD 0.032 Tc 0.107 Tw (Rold\207n G., Delgado L. and Mus\216 I. (2006). Tumoral expression of)Tj 1.65544 -1.42267 TD 0.013 Tc 0.126 Tw (BRCA1, estrogen receptor alpha and ID4 protein in patients with)Tj T* 0 Tc 0 Tw (sporadic breast cancer. Cancer Biol. Ther. 5, 505-510.)Tj -1.65544 -1.42266 TD 0.025 Tc 0.114 Tw (Rosen P.P. and Hoda S.A. (2006). Breast Pathology: Diagnosis by)Tj 1.65544 -1.42266 TD 0 Tc 0 Tw (needle core biopsy. 2nd ed. Lippincott Williams and Wilkins.)Tj -1.65544 -1.42267 TD 0.125 Tw (Rosenfeldt M. and Ryan K. (2011). The multiple roles of autophagy in)Tj 1.6554 -1.4227 TD 0 Tw (cancer. Carcinogenesis 32, 955-963. )Tj -1.6554 -1.4227 TD 0.011 Tc 0.128 Tw (Ross J. (2010). Human epidermal growth factor receptor 2 testing in)Tj 1.6554 -1.4227 TD 0.019 Tc 0.12 Tw (2010: does chromosome 17 centromere copy number make any)Tj T* 0 Tc 0 Tw (difference? J. Clin. Oncol. 28, 4293-4295. )Tj -1.6554 -1.4227 TD 0.044 Tc 0.095 Tw (Ryd\216n L., Jirstr\232m K., Haglund M., St\214l O. and Fern\232 M. (2010).)Tj 1.6554 -1.4227 TD 0.01 Tc 0.129 Tw (Epidermal growth factor receptor and vascular endothelial growth)Tj ET 0 0 0 0 k 307.559 51.023 242.362 637.904 re f BT /F3 1 Tf 7.5 0 0 7.5 320.9748 682.461 Tm 0 0 0 1 k 0.0133 Tc (f)Tj 0.29127 0.00001 TD 0.013 Tc 0.125 Tw (actor receptor 2 are specific biomarkers in triple-negative breast)Tj -0.29127 -1.42267 TD 0.126 Tw (cancer. Results from a controlled randomized trial with long-term)Tj 0 -1.42266 TD -0.0002 Tc (f)Tj 0.27783 0.00001 TD 0 Tc 0 Tw (ollow-up. Breast Cancer Res. Treat. 120, 491-498. )Tj -1.93327 -1.42268 TD 0.028 Tc 0.111 Tw (Sakamoto G. and Honma N. (2009). Estrogen receptor-beta status)Tj 1.65544 -1.42266 TD 0.0012 Tc (i)Tj 0.2232 0.00001 TD 0.001 Tc 0.138 Tw (nfluences clinical outcome of triple-negative breast cancer. Breast)Tj -0.2232 -1.42267 TD 0 Tc 0 Tw (Cancer 16, 281-282.)Tj -1.65544 -1.42267 TD 0.0335 Tc (S)Tj 0.70047 0.00001 TD 0.033 Tc 0.105 Tw (alvucci O., Bouchard A., Baccarelli A., Desch\220nes J., Sauter G.,)Tj 0.95498 -1.42267 TD 0.03 Tc (S)Tj 0.697 0.00001 TD 0.109 Tw (imon R., Bianchi R. and Basik M. (2006). The role of CXCR4)Tj -0.697 -1.42267 TD (receptor expression in breast cancer: a large tissue microarray)Tj -0.0001 Tc (s)' 0.49985 0.00001 TD 0 Tc 0 Tw (tudy. Breast Cancer Res. Treat. 97, 275-283. )Tj -2.15529 -1.42267 TD 0.064 Tc 0.075 Tw (Sanga S., Broom B., Cristini V. and Edgerton M. (2009). Gene)Tj 1.65544 -1.42266 TD -0.0002 Tc (e)Tj 0.55582 0.00001 TD 0 Tc 0.111 Tw (xpression meta-analysis supports existence of molecular apocrine)Tj -0.55582 -1.42268 TD 0.062 Tc 0.077 Tw (breast cancer with a role for androgen receptor and implies)Tj 0 -1.42266 TD -0.0002 Tc (i)Tj 0.22185 0.00001 TD 0 Tc 0 Tw (nteractions with ErbB family. BMC Med. Genomics 2, 59. )Tj -1.87729 -1.42267 TD 0.115 Tw (Sapino A., Righi L., Cassoni P., Papotti M., Gugliotta P. and Bussolati)Tj 1.65544 -1.42267 TD 0.062 Tc 0.076 Tw (G. (2001). Expression of apocrine differentiation markers in)Tj 0 -1.42266 TD -0.0002 Tc (n)Tj 0.55582 0.00001 TD 0 Tc 0.007 Tw (euroendocrine breast carcinomas of aged women. Mod. Pathol. 14,)Tj -0.55582 -1.42267 TD 0 Tw (768-776. )Tj -1.65544 -1.42266 TD 0.0022 Tc (S)Tj 0.66918 0.00001 TD 0.002 Tc 0.137 Tw (app M., Malik A. and Hanna W. (2003). Hormone receptor profile of)Tj 0.98626 -1.42268 TD 0 Tc 0 Tw (apocrine lesions of the breast. Breast J. 9, 335-336.)Tj -1.65544 -1.42267 TD 0.061 Tc 0.078 Tw (Schmitt F., Soares R. and Seruca R. (1998). Bilateral apocrine)Tj 1.65544 -1.42267 TD 0.053 Tc 0.086 Tw (carcinoma of the breast. Molecular and immunocytochemical)Tj T* 0 Tc 0.049 Tw (evidence for two independent primary tumours. Virchows Arch. 433,)Tj T* 0 Tw (505-509. )Tj -1.65544 -1.42267 TD 0.028 Tc 0.111 Tw (Schmitt F.C. and Reis-Filho J.S. (2002). Oncogenes, granules and)Tj 1.65544 -1.42267 TD 0 Tc 0.039 Tw (breast cancer: what has c-myc to do with apocrine changes? Breast)Tj T* 0 Tw (11, 463-465. )Tj -1.65544 -1.42267 TD 0.023 Tc 0.116 Tw (Seal M., Wilson C., Naus G., Chia S., Bainbridge T. and Hayes M.)Tj 1.65544 -1.42267 TD 0 Tc 0.119 Tw ((2009). Encapsulated apocrine papillary carcinoma of the breast--a)Tj T* 0.051 Tc 0.088 Tw (tumour of uncertain malignant potential: report of five cases.)Tj T* 0 Tc 0 Tw (Virchows Arch. 455, 477-483. )Tj -1.65544 -1.42267 TD 0.027 Tc 0.111 Tw (Selim A. and Wells C. (1999). Immunohistochemical localisation of)Tj 1.65544 -1.42267 TD 0 Tc 0.062 Tw (androgen receptor in apocrine metaplasia and apocrine adenosis of)Tj T* 0.012 Tw (the breast: relation to oestrogen and progesterone receptors. J. Clin.)Tj 0 -1.42266 TD 0 Tw (Pathol. 52, 838-841. )Tj -1.65544 -1.42267 TD 0.023 Tc 0.115 Tw (Selim A.G., El-Ayat G. and Wells C.A. (2000). c-erbB2 oncoprotein)Tj 1.65544 -1.42266 TD 0.007 Tc 0.132 Tw (expression, gene amplification, and chromosome 17 aneusomy in)Tj 0 -1.42267 TD 0 Tc 0 Tw (apocrine adenosis of the breast. J. Pathol. 191, 138-142. )Tj -1.65544 -1.42267 TD 0.049 Tc 0.09 Tw (Selim A.G., El-Ayat G., Naase M. and Wells C.A. (2002). C-myc)Tj 1.65544 -1.42268 TD 0.075 Tc 0.063 Tw (oncoprotein expression and gene amplification in apocrine)Tj 0 -1.42267 TD 0.003 Tc 0.136 Tw (metaplasia and apocrine change within sclerosing adenosis of the)Tj T* 0 Tc 0 Tw (breast. Breast 11, 466-472.)Tj -1.65544 -1.42266 TD 0.13 Tw (Shah D., Persaud V. and Coard K. (1980). Apocrine carcinoma of the)Tj 1.65544 -1.42266 TD 0 Tw (male breast. West Indian Med. J. 29, 272-276. )Tj -1.65544 -1.42267 TD 0.087 Tw (Shan L., Yang Q., Nakamura M., Nakamura Y., Mori I., Sakurai T. and)Tj 1.65544 -1.42267 TD 0.094 Tw (Kakudo K. (2000). Active allele loss of the androgen receptor gene)Tj T* 0.031 Tw (contributes to loss of androgen receptor expression in female breast)Tj 0 -1.42266 TD 0 Tw (cancers. Biochem. Biophys. Res. Commun. 275, 488-492. )Tj -1.65544 -1.42267 TD 0.05 Tw (Shao M.M., Zhang F., Meng G., Wang X.X., Xu H., Yu X.W., Chen L.Y.)Tj 1.65544 -1.42267 TD 0.077 Tc 0.062 Tw (and Tse G. (2011). Epidermal growth factor receptor gene)Tj 0 -1.42266 TD 0 Tc 0.135 Tw (amplification and protein overexpression in basal-like carcinoma of)Tj T* 0 Tw (the breast. Histopathology 59, 264-273. )Tj -1.65544 -1.42267 TD 0.044 Tw (Shao M.M., Chan S., Yu A., Lam C., Tsang J., Lui P., Law B., Tan P.H.)Tj 1.65544 -1.42267 TD 0.105 Tw (and Tse G. (2012). Keratin expression in breast cancers. Virchows)Tj T* 0 Tw (Arch. 461, 313-322. )Tj -1.65544 -1.42267 TD 0.136 Tw (Shim H., Jung W., Kim H., Park K. and Cho N. (2006). Expression of)Tj 1.65544 -1.42267 TD 0.11 Tw (androgen receptors and inhibin/activin alpha and betaA subunits in)Tj 0 -1.42266 TD 0 Tw (breast apocrine lesions. APMIS 114, 352-358. )Tj -1.65544 -1.42266 TD 0.027 Tc 0.111 Tw (Simpson P.T., Reis-Filho J.S., Lambros M.B., Jones C., Steele D.,)Tj ET 0 0 0 0 k 45.354 729.071 504.567 14.1729 re f Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.7 0 0 7.7 531.7993 731.757 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (1407)Tj ET 0 0 0 0 k 45.354 716.262 504.567 12 re f Q /GS3 gs /GS2 gs q BT /F4 1 Tf 10.5 0 2.23185 10.5 220.6233 719.6104 Tm 0 Tr 0 0 0 1 k 0 Tc 0 Tw (Apocrine carcinoma of the breast)Tj ET 0 0 0 0 k 45.354 689.417 504.567 25.512 re f Q endstream endobj 29 0 obj << /Length 12574 >> stream /GS0 gs /GS1 gs q /GS2 gs 0 0 0 0 k 45.354 51.023 242.363 637.904 re f Q /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 58.7701 682.461 Tm 0 Tr 0 0 0 1 k -0.0001 Tc (M)Tj 0.83288 0.00001 TD 0 Tc 0.056 Tw (ackay A., Iravani M., Fenwick K., Dexter T., Jones A., Reid L., Da)Tj -0.83288 -1.42267 TD 0.053 Tc 0.086 Tw (Silva L., Shin S.J., Hardisson D., Ashworth A., Schmitt F.C.,)Tj 0 -1.42266 TD -0.0002 Tc (P)Tj 0.66681 0.00001 TD 0 Tc 0.007 Tw (alacios J. and Lakhani S.R. (2008). Molecular profiling pleomorphic)Tj -0.66681 -1.42268 TD 0.068 Tw (lobular carcinomas of the breast: evidence for a common molecular)Tj 0 -1.42266 TD 0.02 Tc (g)Tj 0.57601 0.00001 TD 0.119 Tw (enetic pathway with classic lobular carcinomas. J. Pathol. 215,)Tj -0.57601 -1.42267 TD 0 Tc 0 Tw (231-244.)Tj -1.65544 -1.42267 TD 0.0262 Tc (S)Tj 0.69323 0.00001 TD 0.026 Tc 0.113 Tw (ingh G., Odriozola L., Guan H., Kennedy C. and Chan A. (2011).)Tj 0.96221 -1.42267 TD -0.0002 Tc (C)Tj 0.72183 0.00001 TD 0 Tc 0.125 Tw (haracterization of a novel PTEN mutation in MDA-MB-453 breast)Tj -0.72183 -1.42267 TD 0 Tw (carcinoma cell line. BMC Cancer 11, 490. )Tj -1.65544 -1.42267 TD -0.0001 Tc (S)Tj 0.66687 0.00001 TD 0 Tc 0.018 Tw (\277rlie T., Perou C., Tibshirani R., Aas T., Geisler S., Johnsen H., Hastie)Tj 0.98857 -1.42267 TD 0.037 Tc 0.102 Tw (T., Eisen M., van de Rijn M., Jeffrey S., Thorsen T., Quist H.,)Tj 0 -1.42266 TD -0.0001 Tc (M)Tj 0.83286 0.00001 TD 0 Tc 0.067 Tw (atese J., Brown P., Botstein D., L\277nning P. and B\277rresen-Dale A.)Tj -0.83286 -1.42268 TD 0.135 Tw ((2001). Gene expression patterns of breast carcinomas distinguish)Tj 0 -1.42266 TD 0.0114 Tc (t)Tj 0.28939 0.00001 TD 0.011 Tc 0.127 Tw (umor subclasses with clinical implications. Proc. Natl. Acad. Sci.)Tj -0.28939 -1.42267 TD 0 Tc 0 Tw (USA 98, 10869-10874. )Tj -1.65544 -1.42267 TD 0.073 Tw (S\277rlie T., Tibshirani R., Parker J., Hastie T., Marron J., Nobel A., Deng)Tj 1.65544 -1.42266 TD 0.0498 Tc (S)Tj 0.71677 0.00001 TD 0.05 Tc 0.089 Tw (., Johnsen H., Pesich R., Geisler S., Demeter J., Perou C.,)Tj -0.71677 -1.42267 TD 0 Tc 0.138 Tw (L\277nning P., Brown P., B\277rresen-Dale A.L. and Botstein D. (2003).)Tj 0 -1.42266 TD 0.0291 Tc (R)Tj 0.75111 0.00001 TD 0.029 Tc 0.11 Tw (epeated observation of breast tumor subtypes in independent)Tj -0.75111 -1.42268 TD 0 Tc 0.133 Tw (gene expression data sets. Proc. Natl. Acad. Sci. USA 100, 8418-)Tj 0 -1.42267 TD 0 Tw (8423.)Tj -1.65544 -1.42267 TD 0.041 Tc 0.098 Tw (Steelman L., Navolanic P., Sokolosky M., Taylor J., Lehmann B.,)Tj 1.65544 -1.42267 TD 0 Tc 0.061 Tw (Chappell W., Abrams S., Wong E., Stadelman K., Terrian D., Leslie)Tj T* 0.014 Tc 0.125 Tw (N., Martelli A., Stivala F., Libra M., Franklin R. and McCubrey J.)Tj T* 0.032 Tc 0.106 Tw ((2008). Suppression of PTEN function increases breast cancer)Tj T* 0.026 Tc 0.113 Tw (chemotherapeutic drug resistance while conferring sensitivity to)Tj T* 0 Tc 0 Tw (mTOR inhibitors. Oncogene 27, 4086-4095. )Tj -1.65544 -1.42267 TD 0.014 Tc 0.125 Tw (Syrj\212koski K., Hyytinen E.R., Kuukasj\212rvi T., Auvinen A., Kallioniemi)Tj 1.65544 -1.42267 TD 0.028 Tc 0.111 Tw (O.P., Kainu T. and Koivisto P. (2003). Androgen receptor gene)Tj T* 0 Tc 0.031 Tw (alterations in Finnish male breast cancer. Breast Cancer Res. Treat.)Tj T* 0 Tw (77, 167-170. )Tj -1.65544 -1.42267 TD 0.056 Tc 0.083 Tw (Takeuchi H., Tsuji K., Ueo H., Kano T. and Maehara Y. (2004).)Tj 1.65544 -1.42267 TD 0.028 Tc 0.111 Tw (Clinicopathological feature and long-term prognosis of apocrine)Tj T* 0.005 Tc 0.134 Tw (carcinoma of the breast in Japanese women. Breast Cancer Res.)Tj 0 -1.42266 TD 0 Tc 0 Tw (Treat. 88, 49-54. )Tj -1.65544 -1.42267 TD 0.02 Tc 0.119 Tw (Tan P., Harada O., Thike A. and Tse G. (2011). Histiocytoid breast)Tj 1.65544 -1.42266 TD 0 Tc 0 Tw (carcinoma: an enigmatic lobular entity. J. Clin. Pathol. 64, 654-659. )Tj -1.65544 -1.42267 TD 0.01 Tc 0.129 Tw (Tanaka K., Imoto S., Wada N., Sakemura N. and Hasebe K. (2008).)Tj 1.65544 -1.42267 TD 0 Tc 0.016 Tw (Invasive apocrine carcinoma of the breast: clinicopathologic features)Tj 0 -1.42268 TD 0 Tw (of 57 patients. Breast J. 14, 164-168. )Tj -1.65544 -1.42267 TD (Tavassoli F.A. (1999). Pathology of the breast. 2nd ed. McGraw-Hill.)Tj T* 0.044 Tc 0.094 Tw (Tavassoli F.A., Purcell C.A., Bratthauer G.L. and Man Y. (1996).)Tj 1.65544 -1.42266 TD 0 Tc 0.078 Tw (Androgen receptor expression along with loss of bcl-2, ER, and PR)Tj T* 0.117 Tw (expression in benign and malignant apocrine lesions of the breast:)Tj 0 -1.42267 TD 0 Tw (Implications for therapy. Breast J. 2, 261-269.)Tj -1.65544 -1.42267 TD 0.048 Tw (Trigueros-Motos L., P\216rez-Torras S., Casado F.J., Molina-Arcas M. and)Tj 1.65544 -1.42267 TD 0.003 Tc 0.136 Tw (Pastor-Anglada M. (2012). Aquaporin 3 (AQP3) participates in the)Tj 0 -1.42266 TD 0.006 Tc 0.132 Tw (cytotoxic response to nucleoside-derived drugs. BMC Cancer. 12,)Tj 0 -1.42267 TD 0 Tc 0 Tw (434.)Tj -1.65544 -1.42267 TD 0.041 Tc 0.098 Tw (Tsutsumi Y. (2012). Apocrine carcinoma as triple-negative breast)Tj 1.65544 -1.42266 TD 0.083 Tc 0.347 Tw (cancer: novel definition of apocrine-type carcinoma as)Tj T* 0.017 Tc 0.121 Tw (estrogen/progesterone receptor-negative and androgen receptor-)Tj 0 -1.42267 TD 0 Tc 0 Tw (positive invasive ductal carcinoma. Jpn. J. Clin. Oncol. 42, 375-386. )Tj -1.6554 -1.4227 TD 0.102 Tw (Unal E., Firat A., Gunes P., Kilicoglu G., Gulkilik A. and Titiz I. (2007).)Tj 1.6554 -1.4227 TD 0.035 Tw (Apocrine carcinoma of the breast: clinical, radiologic, and pathologic)Tj T* 0 Tw (correlation. Breast J. 13, 617-618. )Tj -1.6554 -1.4227 TD 0.011 Tc 0.128 Tw (Varga Z., Zhao J., Ohlschlegel C., Odermatt B. and Heitz P. (2004).)Tj 1.6554 -1.4227 TD 0.042 Tc 0.097 Tw (Preferential HER-2/neu overexpression and/or amplification in)Tj T* 0.069 Tc 0.069 Tw (aggressive histological subtypes of invasive breast cancer.)Tj ET 0 0 0 0 k 307.559 51.023 242.362 637.904 re f BT /F3 1 Tf 7.5 0 0 7.5 320.9748 682.461 Tm 0 0 0 1 k -0.0002 Tc (H)Tj 0.72182 0.00001 TD 0 Tc 0 Tw (istopathology. 44, 332-338. )Tj -2.37726 -1.42267 TD 0.015 Tc 0.124 Tw (Vranic S., Tawfik O., Palazzo J., Bilalovic N., Eyzaguirre E., Lee L.,)Tj 1.65544 -1.42266 TD 0.0059 Tc (A)Tj 0.67287 0.00001 TD 0.006 Tc 0.133 Tw (degboyega P., Hagenkord J. and Gatalica Z. (2010). EGFR and)Tj -0.67287 -1.42268 TD 0 Tc 0.035 Tw (HER-2/neu expression in invasive apocrine carcinoma of the breast.)Tj 0 -1.42266 TD -0.0002 Tc (M)Tj 0.83282 0.00001 TD 0 Tc 0 Tw (od. Pathol. 23, 644-653. )Tj -2.48827 -1.42267 TD 0.125 Tw (Vranic S., Gatalica Z., Deng H., Frkovic-Grazio S., Lee L., Gurjeva O.)Tj 1.65544 -1.42267 TD 0.0229 Tc (a)Tj 0.57893 0.00001 TD 0.023 Tc 0.116 Tw (nd Wang Z.Y. (2011a). ER-)Tj ET Q /GS3 gs /GS2 gs q BT /F6 1 Tf 7.5 0 0 7.5 423.9687 618.441 Tm 0 Tr 0 0 0 1 k 0 Tc (a)Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 428.8559 618.441 Tm 0 Tr 0 0 0 1 k 0.0229 Tc (3)Tj 0.57893 0.00001 TD 0.023 Tc 0.116 Tw (6, a novel isoform of ER-)Tj ET Q /GS3 gs /GS2 gs q BT /F6 1 Tf 7.5 0 0 7.5 524.3798 618.441 Tm 0 Tr 0 0 0 1 k 0 Tc (a)Tj ET Q /GS3 gs /GS2 gs q BT /F3 1 Tf 7.5 0 0 7.5 529.267 618.441 Tm 0 Tr 0 0 0 1 k 0.0229 Tc (6)Tj 0.57893 0.00001 TD 0.023 Tc 0.116 Tw (6, is)Tj -28.35124 -1.42267 TD 0.0832 Tc (c)Tj 0.5832 0.00001 TD 0.083 Tc 0.087 Tw (ommonly over-expressed in apocrine and adenoid cystic)Tj -0.5832 -1.42267 TD 0 Tc 0 Tw (carcinomas of the breast. J. Clin. Pathol. 64, 54-57. )Tj -1.65544 -1.42267 TD 0.0342 Tc (V)Tj 0.70122 0.00001 TD 0.034 Tc 0.105 Tw (ranic S., Teruya B., Repertinger S., Ulmer P., Hagenkord J. and)Tj 0.95422 -1.42267 TD 0.019 Tc 0.12 Tw (Gatalica Z. (2011b). Assessment of HER2 gene status in breast)Tj 0 -1.42266 TD 0.027 Tc (c)Tj 0.52705 0.00001 TD 0.112 Tw (arcinomas with polysomy of chromosome 17. Cancer 117, 48-)Tj -0.52705 -1.42268 TD 0 Tc 0 Tw (53. )Tj -1.65544 -1.42266 TD -0.0002 Tc (V)Tj 0.66685 0.00001 TD 0 Tc 0.049 Tw (ranic S., Gatalica Z. and Wang Z.Y. (2011c). Update on the molecular)Tj 0.98859 -1.42267 TD 0.106 Tw (profile of the MDA-MB-453 cell line as a model for apocrine breast)Tj T* 0 Tw (carcinoma studies. Oncol. Lett. 2, 1131-1137. )Tj -1.65544 -1.42266 TD 0.0185 Tc (V)Tj 0.68555 0.00001 TD 0.019 Tc 0.12 Tw (ranic S., Gurjeva O., Frkovic-Grazio S., Palazzo J., Tawfik O. and)Tj 0.96989 -1.42267 TD 0.04 Tc 0.099 Tw (Gatalica Z. (2011d). IMP3, a proposed novel basal phenotype)Tj 0 -1.42266 TD 0.0055 Tc (m)Tj 0.83854 0.00001 TD 0.006 Tc 0.133 Tw (arker, is commonly overexpressed in adenoid cystic carcinomas)Tj -0.83854 -1.42268 TD 0.083 Tc 0.493 Tw (but not in apocrine carcinomas of the breast. Appl.)Tj 0 -1.42267 TD 0 Tc 0 Tw (Immunohistochem. Mol. Morphol. 19, 413-416. )Tj -1.65544 -1.42267 TD 0.046 Tw (Wang Z., Zhang X., Shen P., Loggie B., Chang Y. and Deuel T. (2006).)Tj 1.65544 -1.42267 TD -0.0002 Tc (A)Tj 1.06416 0 Td 0 Tc 0.12 Tw (variant of estrogen receptor-{alpha}, hER-{alpha}36: transduction)Tj -1.06416 -1.42267 TD 0.054 Tc 0.084 Tw (of estrogen- and antiestrogen-dependent membrane-initiated)Tj T* 0 Tc 0 Tw (mitogenic signaling. Proc. Natl. Acad. Sci. USA 103, 9063-9068. )Tj -1.65544 -1.42267 TD 0.078 Tw (Wang Y., Romigh T., He X., Tan M.H., Orloff M., Silverman R., Heston)Tj 1.65544 -1.42267 TD 0.111 Tw (W. and Eng C. (2011a). Differential regulation of PTEN expression)Tj T* 0.036 Tw (by androgen receptor in prostate and breast cancers. Oncogene 30,)Tj T* 0 Tw (4327-4338. )Tj -1.65544 -1.42267 TD 0.01 Tw (Wang L., Zhang Q., Zhang J., Sun S., Guo H., Jia Z., Wang B., Shao Z.,)Tj 1.65544 -1.42267 TD 0.081 Tw (Wang Z. and Hu X. (2011b). PI3K pathway activation results in low)Tj T* 0 Tw (efficacy of both trastuzumab and lapatinib. BMC Cancer 11, 248.)Tj -1.65544 -1.42267 TD 0.055 Tw (Weigelt B. and Reis-Filho J. (2009). Histological and molecular types of)Tj 1.65544 -1.42267 TD 0.089 Tw (breast cancer: is there a unifying taxonomy? Nat. Rev. Clin. Oncol.)Tj 0 -1.42266 TD 0 Tw (6, 718-730. )Tj -1.65544 -1.42267 TD 0.116 Tw (Weigelt B., Horlings H., Kreike B., Hayes M., Hauptmann M., Wessels)Tj 1.65544 -1.42266 TD 0.029 Tc 0.109 Tw (L., de Jong D., Van de Vijver M., Van\325t Veer L. and Peterse J.)Tj 0 -1.42267 TD 0.028 Tc 0.111 Tw ((2008). Refinement of breast cancer classification by molecular)Tj T* -0.011 Tc 0 Tw (characterization of histological special types. J. Pathol. 216, 141-150.)Tj -1.65544 -1.42268 TD 0.012 Tc 0.127 Tw (Weigelt B., Geyer F. and Reis-Filho J. (2010a). Histological types of)Tj 1.65544 -1.42267 TD 0 Tc 0 Tw (breast cancer: how special are they? Mol. Oncol. 4, 192-208. )Tj -1.65544 -1.42267 TD 0.002 Tc 0.137 Tw (Weigelt B., Geyer F.C., Natrajan R., Lopez-Garcia M.A., Ahmad A.S.,)Tj 1.65544 -1.42266 TD 0.011 Tc 0.128 Tw (Savage K., Kreike B. and Reis-Filho J.S. (2010b). The molecular)Tj T* 0 Tc 0.135 Tw (underpinning of lobular histological growth pattern: a genome-wide)Tj 0 -1.42267 TD 0.009 Tc 0.13 Tw (transcriptomic analysis of invasive lobular carcinomas and grade-)Tj T* (and molecular subtype-matched invasive ductal carcinomas of no)Tj T* 0 Tc 0 Tw (special type. J. Pathol. 220, 45-57.)Tj -1.65544 -1.42266 TD 0.046 Tc 0.093 Tw (Wells C. and El-Ayat G. (2007). 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