C-MYC AND P53 ALTERATIONS IN DEVELOPMENT AND PROGRESSION OF UROTHELIAL TUMORS

Carcinogenesis results from irreversible alterations of the physiologi cal balance between protooncogene and tumor suppressor genes. In this study simultaneous investigation of alterations of the c-myc oncogene and the p53 tumor suppressor gene during development and progression o f bladder cancer was performed. 154 paraffin-embedded urothelial speci mens were examined. Normal urothelium (n=16) yielded no alterations. L ow-grade (G1) papillary tumors (n=10) showed no p53 accumulation, but c-myc overexpression in 6 cases. In 3/12 dysplasia specimens p53 accum ulation was detected, while c-myc overexpression was observed in only one case. In carcinoma in situ, c-myc overexpression (7/39) was also l ess frequent than p53 accumulation (12/39). The incidence of p53 accum ulation was slightly higher in muscle-invasive tumors (T2-3) (n=14) th an in T1 (n=24) bladder cancer. In contrast, the number of tumors with c-myc overexpression increased up to 70% in muscle-invasive tumors. A significant correlation between p53 accumulation and tumor progressio n was observed (p<0.0001). The simultaneous analysis of both genes yie lded specific patterns for the different tumor stages. Extension of th is study could provide the base for a new classification of bladder ca ncer based upon the molecular biology of this tumor entity.