MOLECULAR SCREENING OF MULTIFOCAL TRANSITIONAL-CELL CARCINOMA OF THE BLADDER USING P53 MUTATIONS AS BIOMARKERS

Thirteen of 28 patients (46%) with grade 2-3 multifocal transitional c ell carcinoma (TCC) of the bladder were found to have p53 mutations us ing DNA sequence analysis, These were subsequently utilized as tumor-s pecific biomarkers, Analysis of 17 episodes of recurrence from five of the patients revealed that all but one carried the identical mutation to the primary tumor, Thirty urine samples were collected, at initial diagnosis and during follow-up screening, from eight patients with mu tations over a period of 24 months, Sequence analysis of PCR products generated from DNA extracted from the urine sediments was carried out, The p53 mutation seen in the primary tumors was detectable in 24 of 3 0 urine samples, The remaining six cases coincided with a negative cys toscopic examination, Interestingly, 6 of the 24 urine samples in whic h mutations were detectable also coincided with negative cystoscopy, T he results are consistent with: (a) monoclonality of multifocal TCC; ( b) the spread of TCC through a seeding mechanism; and (c) the long-ter m persistence of tumor cell clones (up to 97 months) within the bladde r, even in the absence of obvious tumor growth.