Reduction of BRCA1 expression in sporadic ovarian cancer

Objective. The purpose of this study was to examine BRCA1 expression and it s relationship to cell proliferation in sporadic ovarian epithelial tumors (OETs). Methods. We investigated BRCA1 expression and cell proliferative activity i n 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 investig ated in all 72 cases by immunohistochemistry (IHC). BRCA1 mRNA in fresh fro zen tissue samples from 20 of these cases was measured by a semi-quantitati ve reverse transcription-polymerase chain reaction (RT-PCR) method. Results. The average percentage of BRCA1-positive cells was 5.6% in cystade nomas, 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%), an d grade 3 (0%). The average percentage of MIB-1-positive cells increased st eadily from cystadenomas (7.5%) to borderline tumors (22.6%) to carcinomas (41.2%). BRCA1 expression was highly correlated with MIB-1 expression in cy stadenomas and borderline tumors. Six of seven OECs negative for BRCA1 by I HC showed low levels of BRCA1 mRNA by RT-PCR. Conclusions. BRCA1 expression paralleled cell proliferation in benign and b orderline 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 eti ologic significance in the occurrence and progression of sporadic ovarian c ancer. (C) 2000 Academic Press.