BRCA1 is a tumor suppressor gene which, when mutated, is associated with the development of hereditary breast
cancers. In sporadic
tumors, although inherent gene mutations are rare, loss of BRCA1, resulting from reduced expression or incorrect subcellular localization, is postulated to be important. The purpose of the current study was to examine the expression and localization of
BRCA1 protein and to assess its prognostic value, in a well-characterized series of unselected
breast carcinomas. We have examined BRCA1 in a series of invasive
breast carcinoma (1940 cases) using tissue microarray and immunohistochemistry, to evaluate its expression pattern and to correlate this with clinicopathologic variables and patient outcome. In
breast cancer, complete loss of nuclear expression was observed in 223 cases (15%) and cytoplasmic expression was found in 541 breast
cancers (36.6%). Absent or reduced nuclear BRCA1 expression was observed more frequently in
ductal carcinoma of no special type and medullary-like
carcinoma and less frequently in lobular and tubular mixed
carcinomas. It was also associated with high-grade, advanced lymph node stage, larger size, vascular invasion, negative
estrogen receptor,
progesterone receptor and
androgen receptor expression, and positive p53 and
P-cadherin expression, and with the basal-like class of
breast cancer. Altered BRCA1 was associated with shorter disease-free interval. Cytoplasmic expression was also associated with development of recurrence and positive EGFR and HER2 expression. It showed an inverse association with survival particularly in low-grade, small-size, and
estrogen receptor-positive subgroups. In the grade 1 subgroup, multivariate analysis with adjustment for other prognostic factors showed that cytoplasmic expression of BRCA1 was an independent predictor of disease-free interval. BRCA1 alteration may play a significant role in the development and progression of
breast cancer. Immunohistochemical assessment of BRCA1 expression could provide additional clinically relevant information in routine classification of
breast cancer.