[Neuroendocrine differentiation in prostate cancer: an unrecognized and therapy resistant phenotype]

Neuroendocrine (NE) differentiation frequently occurs in common prostatic malignancies but usually escapes pathological and clinical detection. The present review focuses on biological properties of NE tumor cells making them resistant to androgen deprivation and radiation therapy. Recent data have shown that NE prostate cancer cells (as defined by the most commonly used endocrine marker chromogranin A) are arrested in the G0-phase of the cell cycle and do not undergo apoptosis. This particular phenotype consistently lacks the nuclear androgen receptor in both benign and malignant conditions but produces a series of hormonal growth factors exerting mitogenic stimuli on adjacent, exocrine tumor cells. Neoplastic NE cells devoid of the nuclear androgen receptor constitute an androgen-insensitive cell population in prostate cancer. The absence of proliferative and apoptotic activity makes NE tumor cells particularly resistant towards cytotoxic drugs and radiation therapy. Pathological and clinical detection of NE features is recommended for all prostate cancer patients for whom radiation therapy and androgen deprivation is being considered.