Neutral endopeptidase protein expression and prognosis in localized prostate cancer

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Iman OsmanDavid M Nanus

Abstract

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. 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). 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 con...Continue Reading

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Citations

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