Evidence of functional RB protein in epithelial ovarian carcinomas despite loss of heterozygosity at the RB locus

The presence of retinoblastoma (RB) protein was evaluated by immunohistochemical staining and correlated with loss of heterozygosity (LOH) at the RB locus in 52 primary epithelial ovarian carcinomas. Forty-eight tumors were informative at the RB locus by molecular genetic analysis. Twenty-five tumors (52%) showed loss of heterozygosity at the RB locus. RB protein expression was found in 23 of these tumors. The remaining two tumors were negative for RB protein product by immunohistochemical staining. All 23 tumors showing no LOH at the RB locus had a normal RB protein pattern. All but three tumors revealed either no LOH with any marker or, if LOH was found for one chromosome 13 marker, all other informative markers also showed LOH. The three recombinant tumors included two which retained alleles at one or more loci distal and one which retained alleles proximal to the RB locus. LOH at the RB locus was significantly more common in invasive high-grade (grades 3 and 4) tumors as compared to invasive low-grade (grades 1 and 2) tumors (P < 0.001). Our data suggest that while molecular genetic studies reveal frequent LOH at the RB locus, particularly in high-grade tumors, normal RB protein expression is present in the majority (96%) of these tumors. This implies that another, unidentified, gene or genes located on chromosome 13 may be important in the progression of most epithelial ovarian carcinomas. Additionally, it is likely that the specific chromosome 13 alteration(s) associated with sporadic ovarian neoplasms will be extremely difficult to identify using allelic loss and deletion mapping studies.