Reduced expression of retinoblastoma (Rb) gene protein is related to cell proliferation and prognosis in transitional-cell bladder cancer.

Archival biopsy specimens from transitional-cell bladder cancers (n = 222) were analysed immunohisto-chemically for expression of retinoblastoma (Rb) gene protein. The intensity of staining for Rb protein and the fraction of positive nuclei were analysed and related to several other prognostic factors and survival. Six per cent of the tumours were totally negative for Rb protein and abnormal (weak) expression was found in 40% of cases. The fraction of positive nuclei and abnormal expression (weak) were highly significantly interrelated (P < 0.0001). A low value for the fraction of Rb-protein-positive nuclei was related to a large fraction in S phase (P = 0.001), high mitotic index (P = 0.016) and overexpression of epidermal growth factor receptor (P = 0.034) and p53 protein (P = 0.019). A normal Rb protein expression pattern was related to low S-phase values (P = 0.0001) whereas over-expression of p53 was related to high S-phase values (P = 0.0077). Morphometrically measured nuclear atypia and the fraction of Rb-protein-positive nuclei were negatively correlated (P < 0.05). In univariate survival analysis altered expression of Rb protein (P = 0.07) and low frequency (< or = 50%) of Rb-protein-positive nuclei (P = 0.0128) predicted a poor outcome. In a multivariate analysis, reduced expression of Rb protein had no independent prognostic value over T category, papillary status and the size of the S-phase fraction. The results show that tumor-suppressor genes Rb and p53 participate in the growth regulation of human bladder cancer cells in vivo and accordingly modify the prognosis.