Abstract
Background: Loss of the membrane endopeptidase CD10 plays an important role in the development of neuropeptide-mediated androgen-independent prostate cancer cell growth. The aim of this study was to investigate the potential prognostic value of the CD10/neuropeptide axis with regard to prostate-specific antigen (PSA) failure after radical prostatectomy in early prostate cancer patients. Methods: Tumor samples from 70 early prostate cancer patients who underwent radical prostatectomy were immunohistochemically evaluated for expression of CD10 and endothelin-1 (ET-1). The examined parameters were prospectively correlated with time to PSA failure and combined with Gleason grade and pathological TNM stage. Results: Membranous and apical cytoplasmic expression of CD10 was directly correlated with time to PSA failure ( P < 0.001). Cytoplasmic ET-1 was inversely correlated with time to PSA relapse ( P = 0.002). CD10 and ET-1 were inversely interrelated ( P < 0.001). CD10 expression (P = 0.012) and stage ( P = 0.013) were independent predictors of biochemical recurrence. Conclusion: CD10 and ET-1 follow inverse patterns of expression in tumors of early prostate cancer patients, in accordance with their biological roles and molecular interrelations. Evaluation of CD10 expression in early prostate cancer might contribute to a better prediction of PSA relapse-free survival after radical prostatectomy.
Highlights
The investigation of endothelins, a family of potent vasoconstrictor peptides with mitogenic properties relevant to carcinogenesis and cancer progression, has consistently provided results implicating endothelin-1 (ET-1) in the pathophysiology of prostate cancer
We have investigated the clinical relevance of both CD10 and endothelin-1 (ET-1) in a cohort of hormone-naïve patients subjected to radical prostatectomy for early stage prostate cancer, using the time to biochemical failure as an indicator of response, and taking into account other known prognostic factors, including pathological stage and Gleason score
According to level of CD10 expression, patients were divided into a group of low (n=36) and another of high CD10 expression (n=34)
Summary
The investigation of endothelins, a family of potent vasoconstrictor peptides with mitogenic properties relevant to carcinogenesis and cancer progression, has consistently provided results implicating endothelin-1 (ET-1) in the pathophysiology of prostate cancer. ET-1 exerts its effects through the ET-A receptor subtype, which shows increased expression in prostate cancer. Expression of the ET-B receptor, which mediates ET-1 clearance, is low in prostate cancer, contributing to reduced clearance and sustaining/amplification of ET-1 signaling and autocrine/paracrine growth effects [4,5,6]. It has been postulated that androgens exert a negative role in the regulation of ET-1 production by prostate cancer cells [9]. Loss of the membrane endopeptidase CD10 plays an important role in the development of neuropeptide-mediated androgen-independent prostate cancer cell growth. The aim of this study was to investigate the potential prognostic value of the CD10/neuropeptide axis with regard to prostate-specific antigen (PSA) failure after radical prostatectomy in early prostate cancer patients
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