Clinical implications of p53 mutation analysis in bladder cancer tissue and urine sediment by functional assay in yeast.

Abstract

In the present study we correlate the p53 gene mutations in tumour tissue with urine sediment using a functional assay in yeast, and relate the p53 status to the outcome in a group of patients with transitional cell carcinoma of the bladder. The p53 mutations were found in three of 30 (10%) Ta/T1 tumour tissue samples and in two of 20 (10%) corresponding urine sediments. In the stage T2-T4 tumour p53 mutations were found in tumour tissues and urine sediments in 13 of 31 (42%) and in seven of 18 (39%) samples, respectively. In 80% (8/10) of cases, the p53 mutations found in tumour tissue were re-detected in urine sediment. Median follow-up was at 20 months. Disease recurred in 18 of the 61 patients (30%) with a median time of 5 months. In Ta/T1 tumours the frequency of recurrence was 37% (11/30) compared with 23% (7/31) of T2-T4 tumours. The 3-year overall survival (OS) was 82% (50/61). The p53 status was significantly associated with stage (P = 0.0077, two-sided Fisher's exact test), grade (P < 0.001) and lymph node involvement (P = 0.027). There was an association between the p53 mutations and shorter OS (P = 0.033; log-rank test); however in a multivariate analysis adjusted for stage, grade, lymph node status and age the p53 mutation was not an independent predictor of survival. There was no correlation of the p53 status with decreased disease-free survival (P = 0.8; log-rank test). The data presented indicate that the yeast functional assay is a useful method for p53 gene mutation analysis in tumour tissue and p53 mutation can be re-detected in urine sediment, but further validation of the assay in non-invasive screening for p53 mutations is needed.