[Rudolf Virchow Prize 1997. Molecular cytogenetic analysis of superficial urothelial cancer of the bladder].

Development and progression of urinary bladder cancer is driven by an accumulation of genetic alterations. Most previous molecular and cytogenetic analyses of urinary bladder cancer were focused on advanced tumor stages. To learn more about molecular cytogenetic changes in early bladder cancer stages we analyzed 56 superficial carcinomas of the urinary bladder by comparative genomic hybridization (CGH). CGH is based on the simultaneous hybridization of differentially labeled tumor and normal DNA's to normal metaphase chromosomes. CGH allows the detection of all DNA sequence copy number changes (deletions, DNA sequence copy number gains, amplifications) of a tumor in one examination. Deletions were most frequently found at 9q (20 of 56 patients; 36%), chromosome Y (15 of 43 male patients; 35%), 9p (28%), 11q (16%), 11p (13%), and 10q (11%). DNA sequence copy number gains were most prevalent at 1q (34%), 8q (22%), 17q (15%), 20q (13%), and 12q (11%). There was a significant increase in the number of aberrations with tumor stage (pTa vs. pT1; p = 0.0003) and histologic grade (p = 0.0001). Several specific alterations were significantly more frequent in pT1 than in pTa tumors including deletions at 2q, 8p, and 11p as well as gains at 1q, 3p, 3q, 5p, 6p, 8q, and 10p. These loci are candidates for carrying genes involved in invasive tumor growth in bladder cancer. Overall, these data show that marked genetic differences exist between pTa and papillary pT1 bladder cancer. This challenges the concept of grouping these tumors together in one group as "superficial bladder cancer".