BRAF mutation in breast cancer by BRAF V600E mutation-specific antibody

Abstract

The aim of this study is to investigate the BRAF mutation status using BRAF V600E mutation specific antibody in human breast cancer tissue, and discuss its clinical implications. Immunohistochemical staining for BRAF V600E mutation specific antibody was performed using tissue microarrays of 230 cases of breast cancer and 132 cases of triple-negative breast cancer (TNBC). The cases were subdivided into four molecular subtypes, luminal A, luminal B, HER-2 or TNBC, according to the results of ER, PR, HER-2, Ki-67 immunohistochemistry and HER-2 FISH. In TNBC cases, additional immunohistochemical stain for CK5/6, EGFR, claudin 3, claudin 4, claudin 7, E-cadherin, AR, GGT-1, STAT1, and interleukin-8 were performed. TNBC cases were then further subcategorized as follows: basal-like type (CK5/6 positive and/or EGFR positive), molecular apocrine type (AR positive and/or GGT-1 positive), claudin low type (claudin 3, claudin 4, claudin 7 negative and E-cadherin negative), immune related type (stromal STAT1 positive and IL-8 negative), mixed type (cases consisting of two or more mixed components), and null type (cases that cannot be categorized in any of abovementioned types). In 230 breast cancer, 30 (13.0%) cases showed positivity for BRAF V600E mutation specific antibody, and 17 (7.4%) showed nuclear expression. The nuclear BRAF V600E positivity was associated with ER negativity (P=0.003), PR negativity (P=0.031) and TNBC subtype (P=0.009). In 132 cases of TNBC, 4 (3.0%) cases were positive for BRAF V600E mutation specific antibody, and 10 (7.6%) cases showed nuclear expression. BRAF V600E positivity was most frequently found in the null type, followed by mixed type and basal-like type, and was not found in other subtypes. In TNBC, the nuclear BRAF V600E positivity was associated with lower histological grade (P=0.012). BRAF V600E status did not correlate with the prognosis of breast cancers and TNBC. In conclusion, positivity for BRAF V600E mutation specific antibody was noted in a fraction of breast cancer and TNBC, suggesting the presence of BRAF mutation. BRAF mutation did not have association with clinicopathologic factors of breast cancer.