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

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 less than .001), DNA aneuploidy (P less than .05), and high cell proliferation rate as defined by flow cytometric S-phase analysis (P less than .01) or PCNA expression (P less than .01). High-level p53 accumulation predicted short, progression-free interval (P less than .01) and poor survival (P less than .001), with about a 12-fold relative risk of death 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.