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 contemporary prostate cancer research. Methods: The present review focuses on growth properties and the androgen receptor (AR) status of NE phenotypes, and discusses their morphogenetic origin 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 chromogranin A) do not proliferate or show apoptotic activity. This particular phenotype also lacks the nuclear AR in both benign and malignant conditions. Conclusions: Prostatic NE cells most likely derive from local stem cells and represent terminally differentiated and androgen-insensitive cell populations in benign prostate tissue. The frequent occurrence of NE differentiation in prostatic adenocarcinoma obviously reflects the differentiation repertoire of its stem cells. Neoplastic NE cells devoid of nuclear AR constitute an androgen-insensitive cell population in prostate cancer. The absence of proliferative and apoptotic activity may endow NE tumor cells with relative resistance towards cytotoxic drugs and radiation therapy.