Reduction of BRCA1 Expression in Sporadic Ovarian Cancer

Abstract

Objective. The purpose of this study was to examine BRCA1 expression and its relationship to cell proliferation in sporadic ovarian epithelial tumors (OETs).Methods. We investigated BRCA1 expression and cell proliferative activity in 72 unselected OETs. They comprised 16 benign cystadenomas, 18 borderline (low malignant potential) tumors, and 38 carcinomas (OECs). These patients had no known family history of breast and/or ovarian cancer. BRCA1 and the cell proliferation marker, MIB-1, expressions in fixed tissue were investigated in all 72 cases by immunohistochemistry (IHC). BRCA1 mRNA in fresh frozen tissue samples from 20 of these cases was measured by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method.Results. The average percentage of BRCA1-positive cells was 5.6% in cystadenomas, 29.7% in borderline tumors, and 6.6% in OECs. The average decreased steadily with increasing grade of OECs: grade 1 (21.4%), grade 2 (1.1%), and grade 3 (0%). The average percentage of MIB-1-positive cells increased steadily from cystadenomas (7.5%) to borderline tumors (22.6%) to carcinomas (41.2%). BRCA1 expression was highly correlated with MIB-1 expression in cystadenomas and borderline tumors. Six of seven OECs negative for BRCA1 by IHC showed low levels of BRCA1 mRNA by RT-PCR.Conclusions. BRCA1 expression paralleled cell proliferation in benign and borderline OETs, but not in OECs. Sporadic OECs showed significantly reduced levels, rather than complete loss, of BRCA1 expression. The reduction was closely related to tumor grade. Reduction of BRCA1 expression may be of etiologic significance in the occurrence and progression of sporadic ovarian cancer.