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Co-expression of cancer testis antigens and topoisomerase 2-alpha in triple negative breast carcinomas

Triple negative breast cancers (TNBC) are characterized by aggressive tumor biology, lack of targetedtreatments and poor prognosis. Anthracyclins were shown to induce immunogenic death in target cells, potentially leading to “endogenous” vaccination. We comparatively assessed expression of cancer testisantigens (CTA) and topoisomerase 2-alpha (TOPO2A), a well defined molecular target of anthracyclins, in TNBC fully characterized for basal-like (BL) immunophenotype, BL morphology and conventional clin-icopathological factors. The study included 83 patients undergoing surgery between January 2003 andDecember 2009. Tissue sections were stained with CK5/6, CK14, EGFR, Ki-67, TOPO2A, MAGE-A1, MAGE-A10, NY-ESO and multi-MAGE-A specific reagents. Of the 83 TNBC, >66.3% had BL immunophenotype and48.2% had BL morphology. MAGE-A1 specific staining was most frequently detectable (69.2%), followedby multi-MAGE-A (58%), NY-ESO (27.1%) and MAGE-A10 (16%) specific staining. MAGE-A10 expressionsignificantly correlated with tumor size (p = 0.026). Furthermore, MAGE-A1, MAGE-A10 and multi-MAGE-A specific stainings significantly correlated with advanced clinical stage (p = 0.024, p = 0.041, p = 0.031, respectively). We found no significant association between CTA expression and disease free (DFS) oroverall survival (OS). Most interestingly, a significant correlation was observed between expression ofMAGE-A10 and NY-ESO and expression of TOPO2A (p = 0.005, p = 0.013). Expression of defined CTA andTOPO2A are significantly correlated in TNBC. Considering the limited therapeutic options for TNBC, thesefindings might suggest novel forms of combination therapies that should be further explored.

Basal like breast cancer ; Cancer testis antigens ; Combination treatments ; Topoisomerase 2-alpha ; Triple negative breast cancer ; Human

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