Expression and prognostic value of the cell-cycle regulatory proteins, Rb, p16MTS1, p21WAF1, p27KIP1, cyclin E, and cyclin D2, in ovarian cancer

To investigate the role of cell-cycle regulatory proteins in ovarian cancer, we performed immunohistochemistry for the cell-cycle promoters cyclin E and cyclin D2 and the cell-cycle inhibitors, Rb, p16(MTS1), p21(WAF1), and p27 K-IP1, in 93 ovarian carcinomas (77 with follow-up data). The results were correlated with clinicopathological parameters and the prognostic value was determined by multivariate analysis. Strong Rb and moderate-high cyclin E immunoreactivity in carcinomas were weakly associated with high expression of the proliferation marker Ki67. By Cox's multivariate analysis, advanced stage (p = 0.013), strong Rb expression (p = 0.006), and negative-weak p21 staining (p = 0.011) were independent prognostic indicators of short overall survival, indicating an apparently paradoxical role of the retinoblastoma protein in these tumors. In addition, trends pointing to an association of higher age (p = 0.067) and positive cyclin E immuntoreactivity (p = 0.093) with an unfavorable prognosis were observed.