Differential expression of immune-related markers in breast cancer by molecular phenotypes

Abstract

The purpose of this study is to investigate the relationship between expression of immune-related molecules such as STAT1, CD20, IL-8, IFN-γ, tumor genetic phenotype, and the clinical course of invasive breast cancer. We constructed tissue microarrays from the breast cancers of 727 patients and classified the cases as either luminal A, luminal B, HER-2, or triple negative breast cancer (TNBC) based on standard pathological and clinical classifications using genetic phenotype. Surrogate immunohistochemical stains (STAT1, CD20, IL-8, IFN-γ) and HER-2 FISH were performed on each microarray. Of the 727 patients cases, 303 (41.7 %) were luminal A, 169 (23.2 %) were luminal B, 71 (9.8 %) were HER2+, and 184 (25.3 %) were TNBC. The expression of STAT1 in tumor cells was higher in luminal-type cancers than in HER2+ and TNBC (P < 0.001), and the TNBC-type tumors showed the highest levels of stromal STAT1 expression (P < 0.001), stromal IL-8 expression (P = 0.005), and CD20 index (P < 0.001). Luminal A type tumors showed the lowest expression of these markers. The stromal IL-8 positivity was associated with shorter DFS and OS in ER positive group, HER-2 negative group, and luminal A group (P < 0.05). To conclude, the immune-related molecules, STAT1, IFN-γ, IL-8, and CD20 are differentially expressed and define particular molecular subtypes which correlate with genetically defined types of tumors. High expression of STAT1 in tumor cells is observed in luminal-type tumors, whereas stromal expression of STAT1, stromal IL-8, and IL-8 in tumor cells is the highest in TNBC-type tumors.