Predictive value of molecular alterations for the prognosis of urothelial carcinoma

Accumulation of p53 and C-Myc overexpression are frequently found in advanced urothelial carcinomas. The prevalence and predictive value of both molecular alterations was investigated in 61 patients with superficial urothelial tumors. Distinct patterns of p53 accumulation and C-Myc 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%. Similarly, while p53 accumulation was significantly (p = 0.02) associated with tumor grade, C-Myc overexpression did not correlate with grade. In multivariate analysis, p53 accumulation was found to be an independent predictor of tumor progression (p = 0.0096), whereas C-Myc overexpression did not correlate with the course of disease. Alterations in both markers together predicted neither tumor recurrence nor tumor progression better than p53 accumulation on its own. Sufficient expression of C-Myc may be a general requirement for proliferative competence in urothelial 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 progressive urothelial carcinoma 73% of the recurrent tumors displayed p53 accumulation.