Neuroendocrine cells in benign and malignant prostate tissue: Morphogenesis, proliferation, and androgen receptor status

Abstract

The presence of neuroendocrine (NE) differentiation in benign and neoplastic prostate tissue has attracted increasing attention in contemporary prostate cancer research. The present review focuses on the proliferation and androgen receptor (AR) status of NE phenotypes and their morphogenetic origin in benign and malignant prostate tissue. Recent data have documented phenotype relation between NE cells and other cell lineages in benign and malignant prostate tissue indicating their common origin. NE cell types (as defined by the most commonly used endocrine marker, chromogranin A) do not show evidence of cell proliferation and consistently lack the nuclear AR in both benign and malignant conditions. 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. Furthermore, the absence of proliferation activity may endow NE tumor cells with relative resistance toward cytotoxic drugs and radiation therapy.