Distinct altered patterns of p27(KIP1) gene expression in benign prostatic hyperplasia and prostatic carcinoma Journal Article

  

Authors:	Cordon-Cardo, C.; Koff, A.; Drobnjak, M.; Capodieci, P.; Osman, I.; Millard, S. S.; Gaudin, P. B.; Fazzari, M.; Zhang, Z. F.; Massague, J.; Scher, H. I.
Article Title:	Distinct altered patterns of p27(KIP1) gene expression in benign prostatic hyperplasia and prostatic carcinoma
Abstract:	Background: The p27(KIP1) gene, whose protein product is a negative rgulator of the cell cycle, is a potential tumor suppressor gene; however, no tumor-specific mutations of this gene have been found in humans. This study was undertaken to identify and to assess potential alterations of p27(KIP1) gene expression in patients with benign prostatic hyperplasia (BPH) and patients with prostate cancer. Methods: We analyzed 130 prostate carcinomas from primary and metastatic site, as well as prostate samples from normal subjects and from patients with BPH. Immunohistochemistry and in situ hybridization were used to determine the levels of expression and the microanatomical localization of p27 protein and messenger RNA (mRNA), respectively. Immunoblotting and immunodepletion assays were performed on a subset of the prostate tumors. Associations between alterations in p27(KIP1) expression and clinicopathologic variables were evaluated with a nonparametric test. The Kaplan-Meier method and the logrank test were used to compare disease-relapse-free survival. Prostate tissues of p27(Kip1) null (i.e., knock-out) and wild-type mice were also evaluated. Results: Normal human prostate tissue exhibited abundant amounts of p27 protein and high levels of p27(KIP1) mRNA in both epithelial cells and stromal cells. However, p27 protein and p27(KIP1) mRNA were almost undetectable in epithelial cells and stromal cells of BPH lesions. Furthermore, p27(Kip1) null mice developed enlarged (hyperplastic) prostate glands. In contrast to BPH, prostate carcinomas were found to contain abundant p27(KIP1) mRNA but either high or low to undetectable levels of p27 protein. Primary prostate carcinomas expressing lower levels of p27 protein appeared to be biologically more aggressive (two-sided P = .019 [Cox regression analysis]). Conclusions/Implications: On the basis of these results, we infer that loss of p27(Kip1) expression in the human prostate may be causally linked to BPH and that BPH is not a precursor to prostate cancer.
Keywords:	immunohistochemistry; adult; cancer survival; major clinical study; histopathology; cancer recurrence; protein analysis; animals; cell cycle proteins; mice; mice, knockout; cohort studies; gene expression; prostatic neoplasms; in situ hybridization; gene expression regulation, neoplastic; prostate; cyclin-dependent kinase inhibitor p27; tumor suppressor proteins; immunoblotting; epithelium cell; prostate hypertrophy; prostatic hyperplasia; regression analysis; prostate carcinoma; neoplasms, hormone-dependent; microtubule-associated proteins; humans; human; male; article
Journal Title:	JNCI: Journal of the National Cancer Institute
Volume:	90
Issue:	17
ISSN:	0027-8874
Publisher:	Oxford University Press
Date Published:	1998-09-02
Start Page:	1284
End Page:	1291
Language:	English
PUBMED:	9731735
PROVIDER:	scopus
DOI:	10.1093/jnci/90.17.1284
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0032475438&partnerID=40&md5=2178fffdcca4bd4d9e16093a0c60f934
Notes:	Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/102581