This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Osman, I. Articles by Nanus, D. M. Search for Related Content PubMed PubMed Citation Articles by Osman, I. Articles by Nanus, D. M.

Neutral Endopeptidase Protein Expression and Prognosis in Localized Prostate Cancer

Departments of ¹ Urology, ² Pathology, and ³ Environmental Medicine, New York University Cancer Institute, ⁴ Kaplan Comprehensive Cancer Center, and Departments of ⁵ Urology and ⁶ Medicine, Weill Medical College of Cornell University, New York, New York

Purpose: Neutral endopeptidase (NEP) is a cell-surface peptidase that inactivates neuropeptide growth factors implicated in prostate cancer progression. The clinical significance of decreased NEP expression observed in prostate cancer is unclear. We investigated whether decreased NEP expression in localized prostate cancers is associated with prostate-specific antigen (PSA) relapse after radical prostatectomy.

Experimental Design: NEP expression patterns were examined by immunohistochemistry in 223 men, who underwent radical prostatectomy between 1990 and 2000 at the Veterans Administration Medical Center (New York, NY) with available representative tissues and adequate follow up. We also examined whether hypermethylation of the NEP promoter contributes to down-regulation of NEP protein expression in a subset of patients that showed decreased NEP expression (n = 22).

Results: Three patterns of NEP expression were observed: (a) membranous expression similar to benign prostate epithelium (n = 82; 37%); (b) complete loss of NEP expression in prostate cancer compared with adjacent benign prostate glands (n = 105; 47%); and (c) heterogeneous NEP expression (n = 36; 16%). In a multivariate analysis, complete loss of NEP expression was associated with PSA relapse after controlling for grade, stage, pretreatment PSA, and race simultaneously (hazard ratio, 1.99; 95% confidence interval, 1.13–3.52; two-sided ² P = 0.017). In addition, DNA hypermethylation of the NEP promoter was frequently (73%) identified in a subset of 22 of cases that showed decreased NEP expression.

Conclusion: Our data suggest that decreased NEP expression might contribute to progression of localized prostate cancer after surgery. Data also suggest that methylation is an important mechanism of NEP protein silencing. Larger prospective studies are required for confirmation.

This article has been cited by other articles:

				A. Fleischmann, T. Schlomm, H. Huland, J. Kollermann, P. Simon, M. Mirlacher, G. Salomon, F. H.K. Chun, T. Steuber, R. Simon, et al. Distinct Subcellular Expression Patterns of Neutral Endopeptidase (CD10) in Prostate Cancer Predict Diverging Clinical Courses in Surgically Treated Patients Clin. Cancer Res., December 1, 2008; 14(23): 7838 - 7842. [Abstract] [Full Text] [PDF]

				O. B. Goodman Jr., M. Febbraio, R. Simantov, R. Zheng, R. Shen, R. L. Silverstein, and D. M. Nanus Neprilysin Inhibits Angiogenesis via Proteolysis of Fibroblast Growth Factor-2 J. Biol. Chem., November 3, 2006; 281(44): 33597 - 33605. [Abstract] [Full Text] [PDF]

				A. S Perry, R. Foley, K. Woodson, and M. Lawler The emerging roles of DNA methylation in the clinical management of prostate cancer. Endocr. Relat. Cancer, June 1, 2006; 13(2): 357 - 377. [Abstract] [Full Text] [PDF]