Neuroendocrine differentiation in human prostatic carcinoma

Abstract

Endocrine-paracrine (APUD, neuroendocrine) cells are located in the prostatic ductal and acinar epithelium. These cells are of the open and closed type and have dendritic processes. There is a wide range of secretory granule morphology presumably indicating a variety of different cell "types." Secretory immunoreactive peptides include serotonin, calcitonin (and related peptides), somatostatin, bombesin-like, thyroid-stimulating hormone-like (beta chain), and alpha-glycoprotein chain-like. These cells may function by endocrine, paracrine, neurocrine, and lumencrine mechanisms and play an important regulatory role both during growth and differentiation of the prostate as well as in the secretory process of the mature gland. Neuroendocrine differentiation in prostatic carcinoma is a frequent occurrence and manifests itself in several forms, including (1) small cell carcinoma, (2) carcinoid and carcinoid-like tumors, and (3) conventional adenocarcinoma with focal neuroendocrine differentiation. This latter pattern is the most common, and there is evidence that all or nearly all prostatic adenocarcinomas show at least some focal neuroendocrine differentiation. A review of the world's literature on this topic is included. Neuroendocrine differentiation generally portends a poorer prognosis but may also correlate directly with the grade. There is some evidence to suggest that neoplastic cells with neuroendocrine differentiation are resistant to hormonal therapy. Eutopic and ectopic hormone production may allow screening for prostatic carcinoma and/or monitoring for recurrence of prostatic carcinomas. Finally, the more basic implications of endocrine-paracrine cells and neuroendocrine differentiation are speculated on in reference to prostatic carcinogenesis and autocrine/paracrine tumor growth factor activity.