Expression profile and prognostic importance in prostate lesions of the reverse transcriptase component of human telomerase (hTERT) and of cyclin-dependent kinase inhibitor p57 (p57kip2a)

Abstract

To investigate expression of the reverse transcriptase component of human telomerase (hTERT) and of cyclin-dependent kinase inhibitor p57 (p57(kip2a)) in prostate neoplasms and evaluate the relationship between these proteins and the Gleason score. hTERT and p57(kip2a) antibodies were studied by immunohistochemical methods in 70 prostate adenocarcinomas (33 high-grade and 37 low-grade carcinomas), 29 benign prostate hyperplasias, and 19 prostatic intraepithelial neoplasias (PIN). Only nuclear staining was evaluated with p57(kip2a) whereas both nuclear and nucleolar staining were evaluated with hTERT. Immunohistochemical histologic scores (HSCOREs) of hTERT were significantly higher in the PIN group than in the hyperplasia group (P = 0.03). hTERT HSCOREs were not significantly different between hyperplasias and carcinomas or between low and high-grade carcinomas. p57(kip2a) HSCOREs were significantly higher in hyperplasias than other groups, and in PINS than carcinomas, but did not differ significantly between low and high-grade carcinomas. A significant negative correlation was observed between hTERT and p57(kip2a) (P = 0.007) in the hyperplasia group. No such correlation was found in PINs and carcinomas. This study suggests that p57(kip2a) is down-regulated in the malignant side of the spectrum of prostate carcinogenesis. Loss of p57(kip2a) control on hTERT might have an important role in the development of prostate cancer.