Neuroendocrine differentiation in prostatic carcinoma

BACKGROUND. Information is presented on prostatic neuroendocrine cells and neuroendocrine differentiation in prostatic carcinoma. The prognostic and t herapeutic implications of neuroendocrine differentiation in prostatic carc inoma are reviewed. METHODS. Data are presented that support the intriguing link between neuroe ndocrine differentiation, tumor progression, and androgen-independent prost ate cancer. The hormones, and the receptors, expressed by prostatic neuroen docrine cells are investigated in order to elucidate their significance for prognosis and therapy. RESULTS. The prognostic significance of neuroendocrine differentiation in p rostatic malignancy has been controversial, but recent studies employing ma rkers such as chromogranin A and neuron-specific enolase suggest that neuro endocrine differentiation, as reflected by increased tissue expression and/ or blood levels of these neuroendocrine secretory products, correlates with poor prognosis, tumor progression, and androgen-independence. Since all ma lignant neuroendocrine cells are devoid of androgen receptors and since neu roendocrine phenotypic expression is not suppressed by androgen ablation, c lonal propagation of androgen receptor-negative neuroendocrine cells may pl ay an important role in the pathway towards the androgen-independent state of prostatic carcinoma. This would have significant implications for the tr eatment of prostate cancer, as several of the hormones known to be expresse d by neuroendocrine-differentiated, malignant prostatic cells are potential candidates for drug therapy. A limited number of hormones have been tested in this context, in particular somatostatin, bombesin, and serotonin. CONCLUSIONS. Neuroendocrine differentiation in carcinoma of the prostate ap pears to be associated with poor prognosis, tumor progression, and the andr ogen-independent state, for which there is currently no successful therapy. Therefore, new therapeutic protocols and trials need to be developed to te st drugs based on neuroendocrine hormones and/or their antagonists. An eval uation of this new therapeutic approach against prostatic carcinoma with ne uroendocrine differentiation, including hormone-refractory cancer, is easil y justified, since these tumors are unresponsive to current modes of therap y. (C) 1999 Wiley-Liss, Inc.