Reduced retinoblastoma gene protein to Ki-67 ratio is an adverse prognostic indicator for ovarian adenocarcinoma patients

OBJECTIVE: Alterations in the retinoblastoma gene (RB-1) are common in human neoplasia. However, the clinical significance of the deregulated expression of RB-1 in ovarian cancer remains undefined. We therefore conducted a retrospective investigation to clarify the relationships of RB-1 gene protein (pRb) to the percentage of cycling cells, clinicopathologic variables, other G1 interacting proteins and prognosis of nonbenign epithelial ovarian tumors. METHODS: Paraffin-embedded tissue from 127 nonbenign epithelial ovarian tumors, including 44 of low malignant potential (LMP) and 83 primary ovarian adenocarcinomas, was stained immunohistochemically for pRb, p21(Cip1), p27(Kip1), p53, and Ki-67 antigen (a cell proliferation associated marker). Expression of these markers was correlated with clinicopathologic features and with overall survival of patients with adenocarcinomas. RESULTS: pRb levels were significantly lower in LMP tumors than in carcinomas (P = 0.027). In the latter group, pRb expression decreased with increasing grade (I-II vs III) (P = 0.010), advancing stage (I-II vs III) (P < 0.001), and bulk residual disease (P = 0.014). pRb was not related to Ki-67 expression (P > 0.10) or to overall survival (P > 0.10) but a low pRb to Ki-67 ratio emerged as an important indicator of poor survival in univariate analysis in the entire cohort (P = 0.0076) and in the platinum-treated patients (P = 0.0162) as well as in multivariate analysis, along with histologic type and FIGO stage. CONCLUSIONS: Diminished pRb levels are related to several clinicopathologic indicators of aggressiveness in ovarian adenocarcinomas. More importantly, pRb expression coupled with the percentage of Ki-67 positive cells is a better prognostic marker than pRb, Ki-67, or other G1 interacting proteins and supplements the information gained from traditional prognosticators.