DESCRIPTION: Dr. Czerniak suggests that aggressive urothelial carcinomas are more likely to develop multiple cumulative genetic alterations of known transforming and tumor suppressor genes. He proposes to test this hypothesis by studying human bladder tumors in biopsy, cytologic, and surgical resection specimens for alterations in Ha-ras, p53 and Cip1. Dr. Czerniak will also examine microsatellite loci. Because of the volume and types of surgical and cytologic specimens available to him, Dr. Czerniak will examine a large number of samples. To do this, Dr. Czerniak proposes to work through 3 specific aims. First, Dr. Czerniak will propose to identify the involvement of the stated genes in urinary bladder carcinogenesis. Second, Dr. Czerniak will map the locations of tumors vs. the observed changes in urinary bladder genotype (relative to the genes indicated). This mapping will permit him to correlate the histology of the progression from urothelial dysplasia through exophytic and invasive carcinomas with changes in the cellular genotypes. Finally, Dr. Czerniak will study whether these observed changes have any value in monitoring voided urine for evidence of tumor development. Statistical analyses will be performed by a qualified statistician, and he has enlisted the help of numerous experts in their respective fields to assist with the procurement of appropriate tumor specimens and the analysis of the results.