PREDICTIVE VALUE OF MOLECULAR ALTERATIONS FOR THE PROGNOSIS OF UROTHELIAL CARCINOMA

Accumulation of p53 and C-Myc overexpression are frequently found in a dvanced urothelial carcinomas. The prevalence and predictive value of both molecular alterations was investigated in 61 patients with superf icial urothelial tumors. Distinct patterns of p53 accumulation and C-M yc overexpression were observed in superficial urothelial carcinoma of different stages. For instance, 67% of carcinomata in situ displayed accumulation of p53, but only 44% showed C-Myc overexpression, whereas in pT1 tumors the corresponding percentages were 25 and 75%. Similarl y, while p53 accumulation was significantly (p = 0.02) associated with tumor grade, C-Myc overexpression did not correlate with grade. In mu ltivariate analysis, p53 accumulation was found to be an independent p redictor of tumor progression (p = 0.0096), whereas C-Myc overexpressi on did not correlate with the course of disease. Alterations in both m arkers together predicted neither tumor recurrence nor tumor progressi on better than p53 accumulation on its own. Sufficient expression of C -Myc may be a general requirement for proliferative competence in urot helial tumors, barring its use as a predictive marker. The predictive value of p53 accumulation for tumor progression was further underlined by the finding that in a distinct group of 52 patients with progressi ve urothelial carcinoma 73% of the recurrent tumors displayed p53 accu mulation.