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.