Immunolocalization of BRCA1 protein in normal breast tissue and sporadic invasive ductal carcinomas: a correlation with other biological parameters

AIM: BRCA1, a nuclear phosphoprotein, normally functions as a negative regulator of the cell cycle and may be an active inhibitor of neoplastic progression. Mutation of the BRCA1 gene has been demonstrated in 80% of familial breast cancer. Decreased mRNA levels or aberrant subcellular locations of BRCA1 have been identified in breast cancer lines and in sporadic cases of breast cancer tissues. The expression of BRCA1 in large series of variously differentiated breast carcinomas with correlation with other biological parameters has not been clarified. METHODS AND RESULTS: The BRCA1 expression in normal breast tissue (n = 15) and in sporadic cases of invasive ductal carcinoma (n=108) was determined using immunohistochemistry. BRCA1 expression was correlated with other prognostic parameters including p53, c-erbB-2, bcl-2, oestrogen receptor (ER), histological grade, tumour size, axillary lymph node status and age. BRCA1 was exclusively (100%) localized in the nuclei of normal ductal and lobular epithelia. However, this nuclear expression pattern was variable in breast carcinoma (76.8%). Loss of nuclear BRCA1 expression (22 of 108 cases, 20.4%) correlated well with high histological grade (P<0.025) and bcl-2-negative tumours (P<0.05) and frequently in ER-negative tumours. CONCLUSION: BRCA1 nuclear expression could be considered to represent the normal or physiological phenotype. Complete loss of BRCA1 nuclear expression in breast cancer and its correlation with other poor prognostic markers suggest that BRCA1 expression may play an important role in the pathogenesis and prognosis of sporadic breast carcinoma. Altered BRCA1 phenotype may therefore provide an additional prognostic parameter for breast cancer.