Abstract: Objective To better understand the genetic basis of bladder cancer progression.Methods The study examined the patterns of allelic loss with polymorphic microsatellite markers on chromosomes 9p21(D9S161,D9S171,IFNA),regions of putative tumor suppressor gene p16,and on chromosome 17p13(TP53),the p53 locus,in matched primary and metastatic bladder cancers in 18 patients.All patients underwent cystectomy for bladder cancer and were found to have regional lymph node metastases at the time of surgery.Genomic DNA was obtained from primary cancers and matched synchronous lymph node metastases using a microdissection method.Results The overall frequencies of allelic loss were 78% in primary cancers and 89% in paired metastatic cancers.The frequencies of allelic loss in the primary cancers were 86% with D9S161,67% with D9S171,71% with IFNA,and 80% with TP53.The frequencies of allelic loss in matched metastatic cancers were 100% with D9S161,62% with D9S171,71% with IFNA,and 80% with TP53.An identical pattern of allelic imbalance(allelic loss or retention) at multiple DNA loci was observed in matched primary and metastatic carcinomas in 16(88%) cases.Two case showed allelic loss in the metastases,but not in the primary cancers.Conclusion The patterns of allelic loss at chromosomes 9p21(p16) and 17p13(p53) are generally maintained during cancer progression to metastasis,and identical allelic loss in primary cancers is conserved in paired metastatic carcinomas.These data suggest that these genetic changes may be useful in establishing a diagnosis and determining tumor origins in difficult cases.

Key words: bladder tumor, metastases, microdissection, tumor progression