LOSS OF NUCLEAR BRCA1 EXPRESSION IN BREAST CANCERS IS ASSOCIATED WITHA HIGHLY PROLIFERATIVE TUMOR PHENOTYPE

Recent studies have suggested that BRCA1-associated hereditary breast cancer may be a more aggressive form of disease than sporadic breast c ancer. BRCA1-associated breast cancer has been reported to be signific antly associated with grade 3 disease. Because grade 3 disease indicat es a poor prognosis, this implies that women with a germ-line mutation in BRCA1 who develop breast cancer may have a poorer prognosis than t hose with sporadic disease. However, little is known about the associa tion of BRCA1 expression with biological markers of prognosis. The pre sent study examined the expression of BRCA1 in a total of 40 archival breast tumor specimens from thr ee patient cohorts (sporadic, familial , and early onset breast cancer) to determine localization of the prot ein. Furthermore, BRCA1 staining was compared with expression of marke rs of tumor biology. We found that BRCA1 is generally io located in th e nucleus and the cytoplasm of normal and malignant breast tissue. Nuc lear staining for BRCA1 was observed in most sporadic tumors, but nucl ear BRCA1 was reduced or absent in the majority of familial and early onset breast tumors. Although no correlation was found between nuclear BRCA1 expression and estrogen and progesterone status, significant in verse correlation was found between nuclear BRCA1 and expression of th e proliferation marker Ki-67 (P = 0.01). Our findings suggest that tum ors associated with a germ-line mutation in one of the breast cancer g enes may be highly proliferative and support the view that loss of BRC A1 expression in breast tumors may lead to a more aggressive tumor phe notype. (C) Elsevier Science Inc., 1998.