p63 correlates with both BRCA1 and cytokeratin 5 in invasive breast carcinomas: further evidence for the pathogenesis of the basal phenotype of breast cancer.

ABSTRACT

AIMS: To study the expression of p63, cytokeratin (CK) 5 and CK8/18 in invasive ductal carcinomas and their relationship with BRCA1 and other pathological and immunohistochemical features of clinical significance. METHODS AND RESULTS: Immunohistochemistry with the antibodies p63, CK5, CK8/18, BRCA1, oestrogen receptor, progesterone receptor, p53, c-erbB-2 and Ki67 was performed in 102 formalin-fixed paraffin-embedded samples of invasive ductal carcinomas. The CK5+ cases were submitted to a double-immunolabelling study with p63. There was a strong relationship between CK5 and p63 expression and both markers were associated with hormonal receptor-negative high-grade carcinomas with high proliferative rate. Furthermore, there was coexpression of CK5 and p63 in neoplastic cells, indicating that p63, like CK5, is a marker of the basal phenotype of breast cancer. There was a strong relationship between reduced expression of BRCA1 with both p63 and CK5 expression as well as an inverse correlation between p63 and CK8/18 expression, suggesting that loss of p63 expression is required for the transition between a basal to a luminal phenotype of breast carcinoma. CONCLUSIONS: Since p63 is thought to be a marker of stem cells and may act as an oncogene, our data support the idea that BRCA1 acts as stem cell regulator.