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Prostate. 1999 May;39(2):135-48.

Neuroendocrine differentiation in prostatic carcinoma.

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1
Department of Urology, University Hospitals of Malmö and Lund, University of Lund, Sweden. peranders.abrahamsson@urokir.lu.se

Abstract

BACKGROUND:

Information is presented on prostatic neuroendocrine cells and neuroendocrine differentiation in prostatic carcinoma. The prognostic and therapeutic implications of neuroendocrine differentiation in prostatic carcinoma are reviewed.

METHODS:

Data are presented that support the intriguing link between neuroendocrine differentiation, tumor progression, and androgen-independent prostate cancer. The hormones, and the receptors, expressed by prostatic neuroendocrine cells are investigated in order to elucidate their significance for prognosis and therapy.

RESULTS:

The prognostic significance of neuroendocrine differentiation in prostatic malignancy has been controversial, but recent studies employing markers such as chromogranin A and neuron-specific enolase suggest that neuroendocrine 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 malignant neuroendocrine cells are devoid of androgen receptors and since neuroendocrine phenotypic expression is not suppressed by androgen ablation, clonal propagation of androgen receptor-negative neuroendocrine cells may play an important role in the pathway towards the androgen-independent state of prostatic carcinoma. This would have significant implications for the treatment of prostate cancer, as several of the hormones known to be expressed 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 appears to be associated with poor prognosis, tumor progression, and the androgen-independent state, for which there is currently no successful therapy. Therefore, new therapeutic protocols and trials need to be developed to test drugs based on neuroendocrine hormones and/or their antagonists. An evaluation of this new therapeutic approach against prostatic carcinoma with neuroendocrine differentiation, including hormone-refractory cancer, is easily justified, since these tumors are unresponsive to current modes of therapy.

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