CLINICAL PREDICTIVE VALUE OF P53 AND C-ERBB-2 OVEREXPRESSION IN 54 PATIENTS WITH TRANSITIONAL-CELL CARCINOMA (TCC) OF THE URINARY-BLADDER

Various reports reveal that mutations of the p53 tumor suppressor gene and of the c-erbB-2 proto-oncogene occur in Transitional Cell Carcinomas (TCC) of the bladder, and that they correlate with the established prognostic factors (particularly tumor grading and stage), suggesting their possible clinical use in defining patients prognosis. The aim of this study was to confirm the hypothesis that altered expression patterns of the p53 tumor suppressor gene and of the c-erbB-2 oncogene are associated with disease progression and clinical outcome in bladder TCSS. We examined tissue specimens from surgical resection in 54 patients with primary TCCs of the bladder. Nuclear overexpression of p53 and membrane staining of c-erbB-2 were evaluated by immunohistochemical analysis and the results were correlated with the following parameters: patient age, tumor grading and stage, nodal status, vascular and lymphatic invasion. In our study p53 overexpression was more frequent in invasive (pT2-pT3-pT4) than in superficial (pTa-pT1) tumors, and there were significantly more p53 positive cases in G3 than in G1-G2 cancers. A weaker association was observed for lymphatic and venous invasion. C-erbB-2 overexpression showed a weak correlation with tumor grading, stage, nodal status, lymphatic and venous invasion. In univariate survival analysis, p53 overexpression was significantly correlated with poor outcome (p=0.0000), while c-erbB-2 showed a much weaker relationship with patient survival distribution (p=0,039). In multivariate analysis, c-erbB-2 overexpression showed no prognostic value, while p53 showed a high prognostic value with respect to the fundamental clinico-pathological parameters. Our results confirm that p53 immunoreactivity may be of clinical use to define bladder TCC patients subgroups of different prognosis; on the contrary, c-erbB-2 seems to be less valuable in defining patient outcome.