Clinical sensitivity of p53 mutation detection in matched bladder tumor, bladder wash, and voided urine specimens

BACKGROUND. Mutations in the p53 tumor suppressor gene may correlate with a n increased risk of recurrence and disease progression in patients with bla dder carcinoma. The ability to accurately and sensitively detect p53 mutati ons in cytology specimens may be of benefit in the treatment of bladder car cinoma patients with superficial, minimally invasive disease. METHODS. Genomic DNA was isolated from 49 cases, each of which was comprise d of matched bladder tumor tissue, bladder wash, and voided urine specimens obtained concurrently at a single institution. The genomic DNA was analyze d for mutations in the p53 tumor suppressor gene using a p53 mutation detec tion assay. Automated dideoxy sequencing of mutant specimens also was perfo rmed. RESULTS, Of the 49 cases, 29 (59%) showed no evidence of p53 mutations in t he tumor, bladder wash, or voided urine specimens. Of the remaining 20 case s, 19 showed evidence of mutations in the tumor. Of these 19 p53 mutant bla dder tumors, 16 (84%) were detected in the matched bladder wash and 16 (84% ) were detected in the matched voided urine specimens. One case resulted in the detection of mutant p53 in the voided urine and the bladder wash, but not in the tumor. Analysis of the results between tumor tissue and bladder wash or tumor and voided urine showed 84.2% sensitivity, 96.8% specificity, and 91.8% accuracy. Sequence analysis of the mutant cases showed that the mutations detected in the tumor tissue were the same mutations detected in the bladder wash and the voided urine specimens. CONCLUSIONS. Both voided urine and bladder wash specimens from patients wit h bladder carcinoma were found to provide a high rate of clinical accuracy for the determination of the p53 gene status in patients with bladder tumor s. Cancer 2001; 91:2127-35. (C) 2001 American Cancer Society.