CHARACTERIZATION OF NEUROENDOCRINE DIFFERENTIATION IN HUMAN BENIGN PROSTATE AND PROSTATIC ADENOCARCINOMA

Background. This report describes an immunohistopathologic analysis ch aracterizing the incidence, pattern of distribution, and hormonal cont ent of neuroendocrine (NE) cells in human benign prostate and prostati c adenocarcinoma. Methods. Formaldehyde-fixed, paraffin-embedded mater ial from 15 benign prostates, 31 primary prostatic adenocarcinomas, 16 metastatic lesions, 21 primary tumors treated with short-course dieth ylstilbestrol (DES), and 10 specimens from hormone-refractory patients were examined. NE cells were identified using silver histochemistry a nd a panel of immunohistochemical NE markers (chromogranin-A, serotoni n, neuron-specific enolase), and specific peptide hormone antibodies. Results. NE cells were identified in all benign prostates. NE cells we re identified in 77% of primary untreated adenocarcinomas with no sign ificant differences with respect to pathologic stage. NE cells were fo und isolated and dispersed in the tumor, composing the minority of mal ignant cells. Double-labeling and serial section immunohistochemistry demonstrated the coexpression of prostate-specific antigen (PSA) in NE cells. In addition to serotonin, some tumors expressed multiple hormo ne immunoreactivities. NE cells were identified in 56% of metastatic d eposits, with a similar pattern of distribution. In DES-treated cases, NE cells were found consistently in the adjacent benign epithelium, w hereas 52% of tumors contained NE cells. Hormone-refractory tumors con tained NE cells in 60% of cases. Conclusions. This analysis demonstrat es that a significant proportion of primary and metastatic prostatic a denocarcinomas contain a subpopulation of NE cells, the expression of which does not appear to be suppressed with androgen ablation and does not correlate with pathologic stage. Furthermore, NE cells coexpress PSA, suggesting a common precursor cell of origin. The elaboration of biogenic amines and neuropeptides suggests that NE cells dispersed in prostatic carcinoma may play a paracrine growth-regulatory role.