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 synchronous and/or metachronous multifocal urothelial cancers is due to field defect, intraluminal seeding and implantation, or both. We used a series of 42 cases of multiple urothelial cancers. We performed polymerase chain reaction single-strand conformation polymorphism, DNA sequencing, and immunohistochemical studies on p53 gene mutations in 84 multiple urothelial carcinomas (78 urinary bladder carcinomas and 6 ureteric or renal pelvic carcinomas) from 42 patients. p53 Mutations were detected in 42 (50%) of 84 cancerous tumors from 22 (52%) of the 42 patients and were strongly related to the tumor grade but not to the tumor stage. Nine patients had identical mutations with or without additional mutations in the multiple carcinomas, which suggests that the carcinomas had a common origin. Eleven patients, however, had discordant mutations, and two patients had a mutation in one tumor but not in another, 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 difference 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 spectra in this series might reflect the presence of other possible mutagens in carcinogenesis of multiple urothelial carcinomas.