Neutral endopeptidase protein expression and prognosis in localized prostate cancer

Iman Osman, Herman Yee, Samir S. Taneja, Benjamin Levinson, Anne Zeleniuch-Jacquotte, Caroline Chang, Craig Nobert, David M. Nanus

    Research output: Contribution to journalArticle

    Abstract

    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 χ2 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 NE4 protein silencing. Larger prospective studies are required for confirmation.

    Original languageEnglish (US)
    Pages (from-to)4096-4100
    Number of pages5
    JournalClinical Cancer Research
    Volume10
    Issue number12 I
    DOIs
    StatePublished - Jul 15 2004

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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  • Cite this

    Osman, I., Yee, H., Taneja, S. S., Levinson, B., Zeleniuch-Jacquotte, A., Chang, C., Nobert, C., & Nanus, D. M. (2004). Neutral endopeptidase protein expression and prognosis in localized prostate cancer. Clinical Cancer Research, 10(12 I), 4096-4100. https://doi.org/10.1158/1078-0432.CCR-04-0120