Distinct microsatellite alterations in upper urinary tract tumors and subsequent bladder tumors

Purpose: Although synchronous and/or metachronous tumor development is comm on in urothelial cancer, genetic and biological differences in upper urinar y tract and bladder tumors are unclear. We compared the genetic alteration pattern in multifocal disease in patients with upper urinary tract and subs equent bladder tumors, and those with recurrent bladder tumor. Materials and Methods: Using 21 microsatellite markers on the 8 chromosomal arms 2q, 4p, 4q, 8p, 9p, 9q, 11p and 17p we analyzed 34 tumors from 15 pat ients with upper urinary tract and subsequent bladder disease, and 70 tumor s from 22 with recurrent bladder disease. Results: Judging from the patterns of genetic alterations multifocal tumors were considered to have derived from an identical progenitor cell in 7 of 13 evaluable patients (54%) with upper urinary tract and subsequent bladder tumors, and 16 of 19 (84%) who were evaluable with recurrent bladder tumor . These data confirm the view that seeding or intraepithelial spread is a m ajor mechanism for the multifocal development of urothelial cancer in gener al. However, a discordant microsatellite alteration pattern in multifocal t umors was observed in 6 of 7 patients (86%) with upper urinary tract and su bsequent bladder lesions but in 2 of 16 (13%) with recurrent bladder cancer (p <0.005). Conclusions: Our results imply that upper urinary tract neoplasms may be ge netically more unstable than bladder neoplasms. The implantation of tumor c ells from upper urinary tract to bladder may involve additional and diverse genetic alterations. Furthermore, a considerable number of multifocal uppe r urinary tract and subsequent bladder lesions may arise independently via field cancerization mechanism. Our study indicates that the factors contrib uting to multifocal development are different in the 2 groups.