Clinicopathologic features of molecular subtypes of triple negative breast cancer based on immunohistochemical markers

Abstract

This study was performed to identify molecular subtypes of triple negative breast carcinoma (TNBC) based on immunohistochemical markers. We prepared a tissue microarray from TNBC specimens of 122 patients and performed immunohistochemical staining for cytokeratin (CK) 5/6, epidermal growth factor receptor (EGFR), claudin 3, claudin 4, claudin 7, E-cadherin, androgen receptor (AR), and gammma-glutamyltransferase (GGT1). Based on immunoreactivity, tumors were classified into basal-like (CK5/6 positive and/or EGFR positive), molecular apocrine (AR positive and/or GGT1 positive), claudin low (claudin 3, claudin 4, claudin 7 negative and/or E-cadherin negative), mixed (tumors belonging to two or more subtypes), and null (tumors not matching any other subtypes). The TNBC specimens of 122 patients included 27 basal-like (22.1%), 28 claudin low (23.0%), 12 molecular apocrine (9.8%), 23 mixed (18.9%) and 32 null (26.2%) subtype tumors. The molecular apocrine subtype showed the highest percentage of apocrine differentiation and the lowest Ki-67 labeling index (p<0.001 and p=0.040, respectively). In univariate analysis, tumor cell discohesiveness was related with shorter disease free survival (DFS) and overall survival (OS) (p=0.005, and 0.002, respectively). In multivariate analysis, tumor cell discohesiveness was related with shorter OS and CK5/6 positivity (p=0.018), and claudin 7 positivity (p=0.019) was related with shorter DFS. In conclusion, using immunohistochemical staining for CK5/6, EGFR, claudin 3, claudin 4, claudin 7, E-cadherin, AR, and GGT1, we categorized TNBC into a basal-like subtype, a claudin low subtype, a molecular apocrine subtype, a mixed subtype showing characteristics of two different subtypes, and a null subtype not belonging to any of the subtypes identified.