P53 MUTATIONS IN MULTIPLE UROTHELIAL CARCINOMAS - A MOLECULAR ANALYSIS OF THE DEVELOPMENT OF MULTIPLE CARCINOMAS

The purpose of this study is to assess whether the development of sync hronous and/or metachronous multifocal urothelial cancers is due to he ld defect, intraluminal seeding and implantation, or both, We used a s eries of 42 cases of multiple urothelial cancers. We performed polymer ase chain reaction single-strand conformation polymorphism, DNA sequen cing, and immunohistochemical studies on p53 gene mutations in 84 mult iple urothelial carcinomas (78 urinary bladder carcinomas and 6 ureter ic or renal pelvic carcinomas) from 42 patients. p53 Mutations were de tected in 42 (50%) of 84 cancerous tumors from 22 (52%) of the 42 pati ents and were strongly related to the tumor grade but not to the tumor stage. Nine patients had identical mutations with or without addition al mutations in the multiple carcinomas, which suggests that the carci nomas had a common origin. Eleven patients, however, had discordant mu tations, and two patients had a mutation in one tumor but not in anoth er, a fact that strongly suggests independent origin. Double mutations were observed in 9 (21%) of 42 patients; in these types of mutation, transitions were clearly more frequent than transversions, a differenc e from previously reported spectra of urothelial carcinomas. The data indicate that multiple urothelial carcinomas seem to be either common or of independent origin. In addition, the different p53 mutational sp ectra in this series might reflect the presence of other possible muta gens in carcinogenesis of multiple urothelial carcinomas.