Origin of multifocal carcinomas of the bladder and upper urinary tract: molecular analysis and clinical implications

The simultaneous or metachronous development of multifocal tumors with identical or variable histological features in the urothelial tract in a single patient is a well-known characteristic of urothelial cancer. To explain this phenomenon, two distinct concepts have been proposed: the 'field defect' hypothesis according to which urothelial cells in patients are primed to undergo transformation by previous carcinogenic insults and the 'single progenitor cell' hypothesis, which asserts that the multifocal development is caused by the seeding or intraepithelial spread of transformed cells. Results of recent molecular genetic studies support the 'single progenitor cell' hypothesis, and indicate that the genetic and phenotypic diversity observed in multifocal urothelial tumors is a consequence of clonal evolution from a single transformed cell. An understanding of the mechanism of the heterotopic recurrence of urothelial cancer may provide new prospects for early molecular detection and prevention of heterotopic recurrence of urothelial cancer.