p63 protein expression is rare in prostate adenocarcinoma: Implications for cancer diagnosis and carcinogenesis

Objectives. To examine the expression of the p63 protein in normal, preneop lastic, and neoplastic human prostatic tissue. The p63 gene, a member of th e p53 gene family, is expressed in the basal epithelial cells of multiple o rgans. Irregularities in p63 expression have been associated with epithelia l carcinogenesis. Methods. We performed immunohistochemistry with an anti-p63 antibody on spe cimens from radical prostatectomies, prostate needle biopsies, and metastat ic prostate adenocarcinoma. We analyzed p63 expression in regions of normal prostate, benign prostatic hyperplasia, proliferative inflammatory atrophy (PIA), high-grade intraepithelial neoplasia, and adenocarcinoma. Results. Basal epithelial cells in normal, benign prostatic hyperplasia, an d high-grade intraepithelial neoplasia tissue stained intensely for the p63 polypeptide, but the vast majority of adenocarcinoma specimens from 233 pa tients-66 (94%) of 70 radical prostatectomies, 132 (89%) of 148 prostate ne edle biopsies, and 14 (93%) of 15 metastases-did not. In tumors in which th e adenocarcinoma cells were positive, the staining intensity was weak and o ccurred in less than 1% of the cells. Tumors that stained positive for p63 were more likely to be high grade than those that did not (P <0.0001). Basa l cells in PIA expressed p63, but these cells were sparsely distributed rel ative to the basal cells in the normal glands. Luminal cells in PIA were, i n general, negative for p63. Conclusions. In contrast to normal and preneoplastic prostatic tissue, the vast majority of prostate adenocarcinomas do not express p63. Therefore, p6 3 immunohistochemistry represents a potential novel adjuvant method for fac ilitating the pathologic diagnosis of prostate cancer in prostate needle bi opsies. The selective expression of p63 in normal basal cells, coupled with the finding that p63 null mice fail to develop prostates, provides strong evidence that the basal cells represent prostatic epithelial stem cells. In addition, these findings suggest that p63 may protect prostatic epithelial cells against neoplastic transformation and support the hypothesis that in termediately differentiated cells in the luminal epithelium of PIA are the targets of neoplastic transformation in the prostate. (C) 2001, Elsevier Sc ience Inc.