Semiquantitative morphology of human prostatic development and regional distribution of prostatic neuroendocrine cells

BACKGROUND. The neuroendocrine cells of the human prostate have been relate d to proliferative disorders such as prostatic cancer. Their origin, distri bution, and development have therefore been studied and discussed in terms of current stem cell concepts in the prostate. METHODS. Prostatic tissue specimens (n = 20) from human fetuses (n = 8), pr epubertal and pubertal children (n = 8) and mature men (n = 3) were studied immunohistochemically using antibodies directed against neuroendocrine, ep ithelial as well as secretory markers. Semi-quantitative computer-assisted evaluation of different epithelial and stromal components based on stereolo gical principles was performed on azan-stained sections representative of a ll developmental stages. RESULTS. By the end of gestational Week 9, neuroendocrine (NE) cells appear in the epithelium of the urogenital sinus and are subsequently closely ass ociated with the formation of urethral prostatic buds. The fetal and postna tal distribution pattern of NE cells within the gland is characterized by a relatively constant number of cells per gland similar to prostatic smooth muscle cells. Likewise, a density gradient exists with the highest density in the large collicular ducts and almost no NE cells in subcapsular periphe ral acini. In peripheral ducts, the distribution is random. Maturation of t he NE cells precedes that of the secretory cells by about 10-16 years. CONCLUSIONS. A second prostatic stem cell lineage, different from the uroge nital sinus (UGS)-lineage is hypothesized originating from immature neuroen docrine cells. Being morphologically indistinguishable from the UGS-derived prostatic secretory cell lineage, it gives rise to neuroendocrine cells. T heir presence is apparently important for proliferation regulation of the U GS-derived lineage of the prostate. Prostate 46:108-115. 2001. (C) 2001 Wil ey-Liss, Inc.