The prostatic endocrine-paracrine (neuroendocrine) regulatory system and neuroendocrine differentiation in prostatic carcinoma: a review and future directions in basic research. 1994

P A Di Sant'Agnese, and A T Cockett
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, New York 14642.

Endocrine-paracrine (neuroendocrine, amine precursor uptake and decarboxylation [APUD]) cells of the prostato-urethral region are serotonin and peptide containing regulatory cells, which are part of a dispersed neuroendocrine regulatory system also known as the APUD system. These cells most likely regulate growth and differentiation, as well as the secretory functions of the prostate. Prostatic carcinoma exhibits neuroendocrine differentiation in 3 forms: 1) small cell neuroendocrine carcinoma, 2) carcinoid-like tumors and 3) conventional prostatic adenocarcinoma with focal neuroendocrine differentiation. Small cell carcinoma and carcinoid-like tumors are rather rare (1 to 2% of all prostatic malignancies) and generally pursue an aggressive course. Focal neuroendocrine differentiation in adenocarcinoma is extensive in 10% of the cases and may be present in virtually all adenocarcinomas to a minor degree. There are conflicting studies on the prognostic significance of focal neuroendocrine differentiation in prostatic carcinoma, although several suggest a poor prognosis. The finding that serum neuroendocrine markers predict initial insensitivity to or the development of resistance to hormonal suppression therapy, coupled with the recent observation that androgen receptor is not expressed in neoplastic neuroendocrine cells suggests that neuroendocrine differentiation directly results in resistance to hormonal manipulation therapy. Neuroendocrine differentiation in prostatic carcinoma raises the possibility of innovative modes of treatment. Future directions of research should concentrate on the quantitative analysis of serotonin and various peptides in prostatic malignancy, since high levels of constitutive secretion may not be appreciated by immunocytochemistry, as well as analysis of tumors for receptors to neuroendocrine products, which are necessary for these products to have a functional role. Finally, specific subtypes of neoplastic cells with neuroendocrine differentiation based on serotonin and peptide profiles should be analyzed.

UI MeSH Term Description Entries
D008297 Male Males
D009490 Neurosecretory Systems A system of NEURONS that has the specialized function to produce and secrete HORMONES, and that constitutes, in whole or in part, an ENDOCRINE SYSTEM or organ. Neuroendocrine System,Neuroendocrine Systems,Neurosecretory System,System, Neuroendocrine,System, Neurosecretory,Systems, Neuroendocrine,Systems, Neurosecretory
D011467 Prostate A gland in males that surrounds the neck of the URINARY BLADDER and the URETHRA. It secretes a substance that liquefies coagulated semen. It is situated in the pelvic cavity behind the lower part of the PUBIC SYMPHYSIS, above the deep layer of the triangular ligament, and rests upon the RECTUM. Prostates
D011471 Prostatic Neoplasms Tumors or cancer of the PROSTATE. Cancer of Prostate,Prostate Cancer,Cancer of the Prostate,Neoplasms, Prostate,Neoplasms, Prostatic,Prostate Neoplasms,Prostatic Cancer,Cancer, Prostate,Cancer, Prostatic,Cancers, Prostate,Cancers, Prostatic,Neoplasm, Prostate,Neoplasm, Prostatic,Prostate Cancers,Prostate Neoplasm,Prostatic Cancers,Prostatic Neoplasm
D012106 Research Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. (Webster, 3d ed) Research Priorities,Laboratory Research,Research Activities,Research and Development,Activities, Research,Activity, Research,Development and Research,Priorities, Research,Priority, Research,Research Activity,Research Priority,Research, Laboratory
D002276 Carcinoid Tumor A usually small, slow-growing neoplasm composed of islands of rounded, oxyphilic, or spindle-shaped cells of medium size, with moderately small vesicular nuclei, and covered by intact mucosa with a yellow cut surface. The tumor can occur anywhere in the gastrointestinal tract (and in the lungs and other sites); approximately 90% arise in the appendix. It is now established that these tumors are of neuroendocrine origin and derive from a primitive stem cell. (From Stedman, 25th ed & Holland et al., Cancer Medicine, 3d ed, p1182) Argentaffinoma,Carcinoid,Carcinoid, Goblet Cell,Argentaffinomas,Carcinoid Tumors,Carcinoids,Carcinoids, Goblet Cell,Goblet Cell Carcinoid,Goblet Cell Carcinoids,Tumor, Carcinoid,Tumors, Carcinoid
D002277 Carcinoma A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm and not a synonym for "cancer." Carcinoma, Anaplastic,Carcinoma, Spindle-Cell,Carcinoma, Undifferentiated,Carcinomatosis,Epithelial Neoplasms, Malignant,Epithelioma,Epithelial Tumors, Malignant,Malignant Epithelial Neoplasms,Neoplasms, Malignant Epithelial,Anaplastic Carcinoma,Anaplastic Carcinomas,Carcinoma, Spindle Cell,Carcinomas,Carcinomatoses,Epithelial Neoplasm, Malignant,Epithelial Tumor, Malignant,Epitheliomas,Malignant Epithelial Neoplasm,Malignant Epithelial Tumor,Malignant Epithelial Tumors,Neoplasm, Malignant Epithelial,Spindle-Cell Carcinoma,Spindle-Cell Carcinomas,Tumor, Malignant Epithelial,Undifferentiated Carcinoma,Undifferentiated Carcinomas
D004702 Endocrine Glands Ductless glands that secrete HORMONES directly into the BLOOD CIRCULATION. These hormones influence the METABOLISM and other functions of cells in the body. Endocrine Gland,Gland, Endocrine
D005544 Forecasting The prediction or projection of the nature of future problems or existing conditions based upon the extrapolation or interpretation of existing scientific data or by the application of scientific methodology. Futurology,Projections and Predictions,Future,Predictions and Projections
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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