Evaluation of PARP-1, P-MTOR, cytokeratin 5/6 and cytokeratin 14 expression immunohistochemically in triple negative breast cancer

Triple negative breast carcinomas (TNBCs) are immunohistochemically estrogen receptor (ER), progesterone receptor (PR) and c-erbB2 negative tumors constituting 10-20% of breast carcinomas. Majority of TNBCs are basal-like tumors with basal cytokeratin expression, high proliferative activity and are associated with aggressive behavior. Targeted therapies, including PARP1 and mTOR inhibitors, have been investigated in treatment of TNBCs, as those patients cannot benefit from hormonotherapy and transtuzumab therapy. We aimed to evaluate immunohistochemical expression of PARP1 and p-mTOR in TNBCs as well as immunohistochemical expression of cytokeratin 5/6 and 14 in basal-like subtype. Eighty-two TNBC cases diagnosed in our center between 2005 and 2010 were included in the study. Expressions of PARP1, p-mTOR, cytokeratin 5/6 and 14, morphological parameters and survival analyses were performed. We observed cytokeratin 5/6 expression in 59 patients (72%) and cytokeratin 14 expression in 31 patients (37,8%). Of 82, 14,6% (n=12) showed strong PARP1 positivity, 56,1% (n=46) showed weak-moderate PARP1 positivity as 24 cases (29,3%) did not express PARP1. More than half of the cases (58,5%; n=48) were considered positive for overall p-mTOR expression and 41,5% (n=34) were considered negative for overall p-mTOR expression. Sixty-four (78%) cases were classified as basal-like carcinoma. Nuclear grade was higher in basal-like tumors, compared to non-basal-like tumors. However, no significant statistical difference was found between two groups regarding other morphological parameters and survival. PARP1 and cytokeratin 5/6 positive tumors were high-grade tumors with high proliferative activity. PARP1 staining ratio was 26,16%, staining score was 4,9 among grade 3 tumors (p=0,033/ p=0,035). Also, tumors with high PARP1 expression had high mitotic index (p=0,044). Average expected survival was 106,1 months and 78,4 months for cases with high and low PARP1 expression, respectively. The association between survival and PARP1 expression was notable, however, no statistical significance was found (p=0,706). Our findings, particularly on PARP1 and cytokeratin 5/6 expression, appear to be consistent with literature. However, standard criteria should be established in large study groups to evaluate the effects of p-mTOR and cytokeratin 14 expressions.