ABNORMAL P53 EXPRESSION IS RARE IN CLINICALLY LOCALIZED HUMAN PROSTATE-CANCER - COMPARISON BETWEEN IMMUNOHISTOCHEMICAL AND MOLECULAR-DETECTION OF P53 MUTATIONS

BACKGROUND. We assessed the frequency and molecular basis of p53 mutat ions in clinically localized prostatic adenocarcinoma. METHODS. Prosta te specimens were examined from 100 patients with clinically localized prostatic adenocarcinoma and 13 patients with benign prostatic hyperp lasia (BPH). Mutations producing nuclear accumulation of p53 were dete cted immunohistochemically. Exon-specific mutations were analyzed by p olymerase chain reaction amplification and single strand conformation polymorphism (PCR-SSCP) and sequenced. RESULTS. p53 accumulation was d etected in 5 tumors using antibody DO-1, and in 4 of these using antib ody PAb 1801, but not in BPH. PCR-SSCP detected mutations in all 5 tum ors, with alterations in exon 5 for 1 tumor, exon 6 for 3 tumors, and exon 7 for 1 tumor. An exon 6 mutation was also found in a tumor with no anti-p53 staining. CONCLUSIONS. p53 mutations are uncommon in clini cally localized prostatic adenocarcinoma and absent from BPH. 5 of the 6 mutations were derived from locally invasive, prostate carcinomas, supporting the hypothesis that mutation of p53 is a late:event in pros tate carcinoma progression. (C) 1997 Wiley-Liss, Inc.