THE EXPRESSION OF NEUROPEPTIDES IN HYPERPLASTIC AND MALIGNANT PROSTATE TISSUE AND ITS POSSIBLE CLINICAL IMPLICATIONS

Abstract

We characterized the incidence and pattern of distribution of neuroendocrine differentiated tumor cells in prostatic hyperplastic and carcinomatous tissue, correlated neuroendocrine differentiation with prostate specific antigen (PSA) and assessed whether neuroendocrine cells have value as an independent indicator of poor prognosis in patients with prostate carcinoma. We immunohistochemically evaluated hyperplastic and carcinomatous prostate specimens for chromogranin A, neuron specific enolase and serotonin expressing tumor cells. The expression of various markers in cells was analyzed and correlated with tumor DNA ploidy, disease grade and stage, PSA and clinical course in patients with prostate cancer. Enrolled in our study were 31 patients with hyperplastic prostate tissue and 30 with prostatic carcinoma. Followup in cancer cases was 1 to 9 years (mean 3.7). During followup 9 patients (30%) died of cancer. We noted DNA content aneuploidy in 5 cases (16.7%) of prostate carcinoma. Chromogranin A, neuron specific enolase and serotonin were expressed in 80%, 43% and 77% of cases of prostate carcinoma and in 29%, 10% and 36% of hyperplastic tissue, respectively. Larger prostates had no higher content of various neuroendocrine cells than smaller prostates. There was higher expression of neuropeptides in carcinomatous than in hyperplastic tissue. Of the 3 peptides chromogranin A was significantly related to all parameters, including Gleason score, tumor stage, PSA and patient survival. In addition to PSA, neuron specific enolase was also closely associated with other clinicopathological parameters. Serotonin was significantly related to patient survival only but we noted no correlation with Gleason score, tumor stage or PSA. In regard to factors predictive of patient prognosis expression of the 3 neuropeptides in tumor cells, Gleason score, tumor stage and PSA were closely related to patient survival in this study The growth of hyperplastic prostate tissue is related to neuroendocrine cell activity. The chromogranin A marker has the highest expression in prostate cancer. Neuroendocrine cells may represent an independent indicator of poor prognosis in patients with prostate carcinoma.