Evaluation and clinical value of neuroendocrine differentiation in human prostatic tumors

BACKGROUND: Prostate cancer, like other solid tumors, is a rather heterogeneous entity. More than 50% of all malignant prostatic tumors contain neuroendocrine-like cells, which cannot be attributed to small cell prostatic carcinoma or carcinoid-like tumors, which represent only 1-2% of all prostatic malignancies. Several investigators have reported that histopathologic determination of neuroendocrine differentiation in prostate carcinomas may have prognostic implications, while others have not confirmed these results. However, on the basis of experimental data, neuroendocrine-like cells appear to be involved in the emergence of androgen-independent cells and could be a target for new prostate cancer therapeutic strategies. METHODS: The literature on the neuroendocrine phenotype of prostatic carcinoma is reviewed. This review summarizes most of the accumulated experimental and clinical data on the neuroendocrine phenotype in prostate cancer. We analyze the putative functions of neuroendocrine-like cells in prostate cancer progression and discuss the place of neuroendocrine phenotype biomarkers as diagnostic and prognostic factors in prostate cancer. RESULTS: The fact that focal, patchy and heterogeneous clusters of neuroendocrine-like cells are frequently identified in organ-confined prostatic carcinoma probably accounts for the various evaluations of the predictive value of neuroendocrine histological patterns for the clinical outcome at this stage of the disease. The amount of neuroendocrine cells required to produce a detectable elevation in plasma chromogranin A has not yet been determined, but it is correlated with the number of chromogranin A-positive neuroendocrine (NE) cells. Despite the obvious current limitations of the application of neuropeptides as a serological test, this overview will try to more accurately define the possible roles of specific neuropeptides as prostatic cancer markers in diagnostic and monitoring protocols. The plasma chromogranin A level, in comparison with neuron-specific enolase (NSE), chromogranin B (CBG), pancreastatin, or secretogranin levels, appears to be the most useful neuroendocrine marker for determination of neuroendocrine differentiation of advanced prostatic adenocarcinoma. CONCLUSIONS: Future studies on neuroendocrine should confirm whether neuroendocrine biomarkers, especially the chromogranin family of peptides, can be used as prognostic markers during the course of prostate cancer or for the selection of patients suitable for evaluation of new antineoplastic drugs known to be active against specific and aggressive subpopulations of tumor cells.