NEUROENDOCRINE DIFFERENTIATION IN PROSTATIC INTRAEPITHELIAL NEOPLASIAAND ADENOCARCINOMA

Neuroendocrine cells are thought to have a regulatory role in prostati c epithelial growth and may be prognostically useful in prostatic aden ocarcinoma. To determine the extent of neuroendocrine differentiation in high-grade prostatic intraepithelial neoplasia (PIN), a putative pr ecursor of cancer, we studied the immunohistochemical expression of 10 markers in 26 radical prostatectomy specimens with PIN and adenocarci noma. Expression was measured as mean percent of positive cases and po sitive high-power (x40) fields. The highest percentage of cases showed immunoreactivity for serotonin (73%, PIN; 54%, carcinoma), neuron-spe cific enolase (NSE) (67%, PIN; 46%, carcinoma), chromogranin (62%, PIN ; 65%, carcinoma), and human chorionic gonadotropin (hCG) (30%, PIN; 2 2%, carcinoma); the remaining markers showed immunoreactivity in fewer than 5% of cases (somatostatin, calcitonin, corticotropin) or in no c ases (thyrotropin, prolactin, and glucagon). At least one of the marke rs was present in 88% of cases of PIN and 92% of carcinoma. Non-neopla stic epithelial cells expressed serotonin, NSE, chromogranin, and hCG in every case, and the expression was significantly greater than in PI N and cancer. Stepwise regression analysis revealed the following posi tive correlations: chromogranin expression in PIN and patient age, NSE expression in cancer and number of lymph node metastases, and hCG exp ression in cancer and percentage of Gleason pattern 5; serotonin expre ssion in PIN and cancer did not correlate with any of the clinical and pathologic factors. Neuroendocrine differentiation is downregulated i n prostatic carcinogenesis, with intermediate levels of expression in PIN compared with normal cells and carcinoma.