Immunohistochemical profile of triple negative breast cancers: SOX10 and AR dual negative tumors have worse outcomes.

Abstract

Triple negative breast cancer (TNBC) refers to an estrogen receptor negative, progesterone receptor negative, and HER2-negative breast cancer. Although accepted as a clinically valid category, TNBCs are heterogeneous at the histologic, immunohistochemical, and molecular levels. Gene expression profiling studies have molecularly classified TNBCs into multiple groups, but the prognostic significance is unclear except for a relatively good prognosis for the luminal androgen receptor (LAR) subtype. Immunohistochemistry (IHC) has been used as a surrogate for basal and luminal subtypes within TNBC, but prognostication of TNBC using IHC is not routinely performed. We aimed to study immunophenotypic correlations in a well-annotated cohort of consecutive TNBCs, excluding post-neoadjuvant chemotherapy cases. Tissue microarrays were constructed from a total of 245 TNBC cases. IHC stains were performed and consisted of luminal (AR, INPP4B), basal (SOX10, Nestin, CK5, EGFR), and diagnostic (GCDFP15, mammaglobin, GATA3, TRPS1) markers. Survival analysis was performed to assess the significance of clinical pathologic variables including age, histology, grade, lymphovascular invasion [LVI], Nottingham prognostic index [NPI] category, AJCC stage, stromal tumor-infiltrating lymphocytes at 10% increment, CD8+ T-cell count, Ki-67 index, PD-L1 status, and chemotherapy along with the results of IHC markers. Apocrine tumors show prominent reactivity for luminal markers and GCDFP15 while no special type carcinomas are often positive for basal markers. TRPS1 is a sensitive marker of breast carcinoma but shows low or no expression in apocrine tumors. High AJCC stage, lack of chemotherapy, and dual SOX10/AR negativity are associated with worse outcomes on univariable as well as multivariable analysis. LVI and higher NPI category were associated with worse outcomes on univariable but not multivariable analysis. The staining for IHC markers varies based on tumor histology which may be considered in determining breast origin. Notably, we report that SOX10/AR dual negative status in TNBC is associated with a worse prognosis along with AJCC stage, and chemotherapy status.