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Clinical validity of compartmental analysis of tumor-infiltrating lymphocytes (TIL) in triple negative breast cancer (TNBC) - the key is in spatial morphology?

INTRODUCTIONAnalyzes reported to date on TIL in TNBC have evaluated mostly stromal (sTIL) and possibly intratumoral TIL (iTIL), but none evaluated TIL spatially, separately in compartments of central tumor (CT) and invasive margin (IM). Also, none evaluated connection between TIL and other clinicopathological factors. METHODSWe retrospectively analyzed consecutive sample of 152 early TNBC patients treated at our institution 2009-2012. TIL were assessed morphologically, by hematoxylin - eosin (HE), using standard formalin - fixed - paraffin - embedded (FFPE) samples, according to recommendation of International Working Group for Evaluation of TIL, both sTIL and iTIL, spatially, in compartments of CT and IM. Available clinicopathological variables were analyzed, and correlations of all paramethers were calculated. RESULTSMorphological analysis of TIL spatially by compartments showed as follows: median overall sTIL content was 19%, iTIL 5%, TIL in CT 5%, TIL at IM 18%, sTIL in CT 5%, iTIL in CT 1%, sTIL at IM 30%, and iTIL at IM 5%. Intermediate or high TIL content, defined as ≥10% was present in 48% cases of sTIL in CT, 23% of iTIL in CT, 86% of sTIL at IM, and in 47% of iTIL at IM cases. Quarter of patients had TIL>50% in any of four compartments. There was statistically significant positive correlation between sTIL in CT and age and menopausal status, and also tumor size (T), but w/out correlation to histologic subtype, nodal (N) status, grade, and Ki67 ; iTIL in CT were statistically significantly positively correlated to histologic subtype (precisely to NOS subtype), but negatively to age and menopausal status, exactly opposite to sTIL in this section, and w/out correlation to other tumor characteristics, such as T, N, grade or Ki67 ; sTIL on IM, as well as iTIL on IM, showed statistically significant correlation to grade and Ki67, and no correlation to age and menopausal status. DISCUSSIONSection analysis reveals higher density of TIL content at IM, which directs attention towards this neglected tumoral compartment and it's possible role. It also shows, although in small numbers, that possibly iTIL, especially those at IM, could actually not only, as thought so far, serve as , , satellites“ to sTIL, but an entirely autonomous, and even opposite biomarker. Moreover, all that could be concluded from just a simple and cheap HE morphological analysis of standard tumor specimen.

Triple negative breast cancer, tumor-infiltrating lymphocytes, compartment

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