ASSOCIATION OF P53 NUCLEAR OVEREXPRESSION AND TUMOR PROGRESSION IN CARCINOMA IN-SITU OF THE BLADDER

We investigated the prevalence and clinical relevance of p53 nuclear o verexpression, as detected by antibody PAb1801 and immunohistochemistr y, in 33 patients with carcinoma in situ of the bladder. Median follow up was 124 months. Disease progressed in 16 patients (48%) during foll owup. The association between p53 nuclear overexpression and tumor pro gression was assessed by multivariate analysis, controlling for possib le confounding variables, such as patient age and sex, presence of ass ociated stage Ta bladder tumor and adjuvant bacillus Calmette-Guerin t herapy. Patients were stratified into 2 groups according to the per ce nt of tumor cells displaying p53 nuclear overexpression: group 1-18 wi th less than 20% tumor cells positive and group 2-15 with 20% or more tumor cells positive. Disease progressed in 3 patients (16.7%) in grou p 1 and in 13 (86.7%) in group 2 (p <0.0001). Detection of p53 nuclear overexpression in 20% or more tumor cells was the only independent ma rker of tumor progression in univariate and multivariate analyses (p = 0.004, adjusted relative risk 8.6, 95% confidence interval 2 to 40). Death specifically from bladder cancer was also associated with this a ltered pattern of p53 expression (p = 0.01, Fisher's exact test). We c onclude that p53 nuclear overexpression is an early event in bladder c ancer, occurring in 48% of cases of carcinoma in situ of the bladder. Our results also suggest that p53 nuclear overexpression offers signif icant clinical information and may be a useful tool in the selection o f therapy for patients with carcinoma in situ of the bladder.