Small Subgroup of Aggressive, Highly Proliferative Prostatic Carcinomas Defined by p53 Accumulation

Abstract

Background : Mutations in the p53 gene resulting in the accumulation of altered p53 proteins with prolonged half-life have been found in a large variety of human malignancies. Purpose : We studied the significance of p53 protein accumulation in prostatic carcinoma. Methods : The material consisted of 137 paraffin-embedded, primary prostatic carcinomas. Accumulation of p53 protein was studied by immunohistochemical staining using a polyclonal p53-specific CM-1 antibody. Proliferation activity was determined by DNA flow cytometry and by immunohistochemical detection of proliferative cell nuclear antigen (PCNA) using a monoclonal PC10 antibody. Results : Eight (6%) of the tumors showed intense p53 staining in more than 20% of the tumor cells, 15 (11%) had only lower level immunoreactivity, and 114 (83%) showed no staining. High-level p53 accumulation was associated with high histologic grade ( P >.001), DNA aneuploidy ( P >.05), and high cell profieration rate as defined by flow cytometric S-phase analysis ( p >.01) or PCNA expression ( P >.01). High-level p53 accumulation predicted short, progression-free interval ( P >.01) and poor survival ( P >.01), with about a 12-fold relative risk of deatha as compared with p53-negative cases. Low-level p53 accumulation had no prognostic significance. Conclusions: Accumulation of p53 confers proliferative advantage for prostatic carcinoma cells and defines a small subgroup of highly malignant carcinomas. (J Natl Cancer Inst 84:883–887, 1992]