P53 NUCLEAR OVEREXPRESSION AND DISEASE PROGRESSION IN TA-BLADDER CARCINOMA

This study investigates the prevalence and clinical relevance of nuclear overexpression of the p53 protein, as detected by antibody PAb1801, in 54 patients with pathologically confirmed Ta bladder carcinomas obtained by transurethral resection at Memorial Sloan-Kettering Cancer Center between 1972 and 1980. No patient received any prior adjuvant therapy. Clinical and histopathological prognostic variables such as age, sex and tumor grade were also analyzed. The median follow-up was 110 months. Patients were stratified into two groups according to the percent of tumor cells with nuclear overexpression of the p53 protein. Group A included carcinomas with less than 20% (n=42) and Group B with 20% or more (n=12) of tumor cells with positive nuclear immunoreactivity. Five patients of Group A (12%) developed tumor progression as did 7 (58%) patients of Group B (p=0.002). Three (7%) patients of Group A and 3 (25%) patients of Group B died of bladder cancer (p=0.12). This study demonstrates a relatively low prevalence of altered p53 expression in this early stage of bladder cancer (22%). Nuclear overexpression of the p53 protein in greater-than-or-equal-to 20% tumor cells,was highly associated with tumor grade (p=0.01), but the former was the only independent marker of tumor progression (p=0.0008) on the basis of the multivariate analysis performed. It was also the only independent variable . associated with death due to bladder cancer (p=0.04). We conclude that p53 nuclear overexpression is a prognostic indicator in this disease, and may be useful for selection of therapy for patients with non-invasive papillary superficial bladder carcinoma.