Neuroendocrine differentiation in human prostate cancer. Morphogenesis, proliferation and androgen receptor status

Background: The frequent occurrence of neuroendocrine (NE) differentiation in common prostatic malignancies has attracted increasing attention in cont emporary prostate cancer research. Methods: The present review focuses on growth properties and the androgen r eceptor (AR) status of NE phenotypes, and discusses their morphogenetic ori gin in benign and malignant prostate tissue. Results: Recent data have documented a phenotype link between NE cells and other cell lineages encountered in benign and malignant prostate tissue. NE tumor cells (as defined by the most commonly used endocrine marker chromog ranin A) do not proliferate or show apoptotic activity. This particular phe notype also lacks the nuclear AR in both benign and malignant conditions. Conclusions: Prostatic NE cells most likely derive from local stem cells an d represent terminally differentiated and androgen-insensitive cell populat ions in benign prostate tissue. The frequent occurrence of NE differentiati on in prostatic adenocarcinoma obviously reflects the differentiation reper toire of its stem cells. Neoplastic NE cells devoid of nuclear AR constitut e an androgen-insensitive cell population in prostate cancer. The absence o f proliferative and apoptotic activity may endow NE tumor cells with relati ve resistance towards cytotoxic drugs and radiation therapy.