Expression of enhancer of zeste homolog 2 and cytokeratin 5/6 in triple negative versus non-triple negative breast cancer: An immunohistochemical study.

Abstract

Background: Triple negative breast cancer (TNBC) lacks the benefit of a specific target therapy, so identification and evaluation of new therapeutic agents is a high priority. Enhancer of zeste homolog 2 (EZH2) is a putative stem cell marker involved in cell cycle regulation and was linked to aggressive breast cancer. Cytokeratin 5/6 (CK5/6) is a basal cytokeratin used to define basal like breast cancer. The aim: The aim of this work is to investigate the expression of enhancer of EZH2 and CK5/6 in triple negative in comparison with non-triple negative breast cancer using immunohistochemistry. Methods: EZH2 and CK5/6 were retrospectively analyzed by immunohistochemistry in 44 paraffin-embedded specimens of breast cancer patients (20 cases of triple negative and 24 of non-triple negative breast cancer). Results: TNBC was significantly associated with higher grade (p=0.001), high tumor budding (p=0.029), syncytial growth pattern (p=0.002), lymphovascular invasion (p=.0012), geographic necrosis (p=0.003) and lymphocytic infiltrate (p=.001). EZH2 expression is significantly associated with TNBC in comparison with non-TNBC (P=0.001). CK5/6 expression was observed in 75% of cases of TNBC in comparison to 30% of non-TNBC with a statistically significant relation between CK5/6 expression and TNBC (P=0.004). Among cases of TNBC, CK5/6 expression was significantly associated with lymph node metastasis and high tumor budding. Conclusion: Triple negative breast cancer has distinctive but not pathognomonic morphological features. EZH2 was highly expressed in TNBC in comparison with non-TNBC and this may explain the aggressiveness of triple negative breast cancer. Basal breast cancer, identified by CK5/6 expression, showed characteristic features in the form of high tumor budding, marked lymphocytic infiltrate and higher incidence of lymph node metastasis. This finding indicates that CK5/6 positive expression in TNBC is associated with poor prognostic characteristics.