AN UNCERTAIN ROLE FOR P53 GENE ALTERATIONS IN HUMAN PROSTATE CANCERS

Inactivation of the p53 gene has been implicated in prostate cancer pr ogression. To determine the role of p53 inactivation in the progressio n of clinical prostatic carcinomas, we assessed 67 tumors derived from patients with clinically localized disease for chromosome 17p and p53 gene allelic loss, p53 gene mutations using single-strand conformatio nal polymorphism and direct sequencing, and p53 protein expression usi ng immunohistochemical staining, Of 55 informative tumors, 10 demonstr ated loss of 17p or the p53 gene; however, only a single tumor had a m utation in its remaining p53 allele. Significant p53 overexpression wa s observed in 2 of 38 tumors, and 9 others had faint staining of a few nuclei (<1%). p53 overexpression occurred in no informative tumor wit h allelic loss or mutation. In a 1-7-year follow-up, positive immunohi stochemical staining did not confer an increased risk of recurrence (r isk of recurrence, 0.86, P = 0.78), whereas allelic loss of chromosome 17p appeared to be highly correlated with recurrence (risk of recurre nce, 3.7, P = 0.003). In an unrelated group of 42 patients with metast atic prostate cancer, p53 overexpression was found in 26 tumors (62%), and 15 (36%) had high grade staining. Neither the presence nor the de gree of expression correlated with time to progression or time to deat h. This series suggests that p53 gene inactivation is rare in primary prostatic tumors, not essential to the development of prostate cancer metastases, and of limited use as a prognostic marker in patients with primary or metastatic disease. Another gene or genes on chromosome 17 p may be involved in prostate cancer progression.