NEUROENDOCRINE DIFFERENTIATION IN PROSTATIC-CARCINOMA - RECENT FINDINGS AND NEW CONCEPTS

Neuroendocrine cells of the prostate are intraepithelial regulatory cells that probably modulate both growth and differentiation as well as the exocrine secretory process. These cells form a component of the more generalized multiorgan regulatory system known as the amine precursor uptake and decarboxylation (APUD), or dispersed neuroendocrine system. The prostatic neuroendocrine cells contain serotonin and a variety of regulatory neuroendocrine peptides. Neuroendocrine differentiation in prostatic carcinoma is manifested as the relatively rare small cell carcinoma and the much more common, if not ubiquitous, focal neuroendocrine differentiation in conventional prostatic carcinoma. Neuroendocrine differentiation may have diagnostic, prognostic, and therapeutic implications. Recent findings include the expression of parathyroid hormone-related protein, the chromogranin peptide family, epidermal growth factor receptor, and c-erbB-2 immunoreactivity by prostatic neuroendocrine cells. Immunoreactive androgen receptor is not expressed by benign or malignant prostatic neuroendocrine cells. Non-neuroendocrine proliferation foci and bcl-2 immunoreactive cells appear to cluster around neuroendocrine cells in prostatic carcinoma. These findings, along with additional clinical and experimental evidence, suggest that neuroendocrine cells may play a role as an independent prognostic factor in prostate cancer, particularly those that are resistant to hormonal therapy. The therapeutic implications of prostatic neuroendocrine differentiation are discussed as are potential lines of investigation.