ACCUMULATED ALLELIC LOSSES IN THE DEVELOPMENT OF INVASIVE UROTHELIAL CANCER

To investigate the roles of allelic loss in the development of urothelial cancer, loss of heterozygosity was examined on 7 chromosomal arms in 49 cases of urothelial cancer of various grades and stages. Loss of heterozygosity was found on alleles in order of frequency as follows: 9q (21/38, 55%), 11p (20/44, 45%), 17p (18/42,43%),13q (10/39, 26%), 3p (8/41, 20%), 10q (2/29, 7%) and Ip (1/36, 3%). Invasive (high-grade or greater-than-or-equal-to pT2) tumors showed the loss of 17p (1 3/16, 8 1 %) and the loss of 13q (7/16, 44%) with significantly higher frequencies than noninvasive (grade 1-2 less-than-or-equal-top TI) tumors. Although the loss of 3p and the loss of 11p were also more frequently associated with the invasive phenotypes, the loss of 11p was detected in a considerable number (9 of 26, 35%) of non-invasive tumors. Our results indicate that the loss of 11p might generally occur at an earlier stage before the loss of 3p, 13q or 17p in tumor progression. Since no correlation was found between the loss of 9q and the tumor grade or stage, this genetic alteration appears to be unrelated to invasiveness, and could be one of the initial events in tumorigenesis. Although accumulated allelic losses of 3p, 11p, 13q and 17p are considered to be involved in the development of the invasive type of urothelial cancers, these multiple genetic alterations may have already occurred in some pathologically non-invasive urothelial cancers. Furthermore, there appears to be some variation in the pattern of cumulative allelic loss.