Neuroendocrine Differentiation
in Prostatic Carcinoma
Focal neuroendocrine differentiation is present
in virtually all prostate cancers but is prominent in only
5-10%. This neuroendocrine differentiation is a recapitulation
of normal differentiation pathways, albeit in caricature. Some
carcinomas are completely differentiated along neuroendocrine
lines, most notably some small cell carcinomas which are relatively
rare. Neuroendocrine differentiation
may increase with androgen deprivation and neuroendocrine factors
appear to be paticularly active in androgen independent prostate
cancer. Interestingly, neuroendocrine cells, both benign and
malignant, do not express androgen receptor, in contrast to
non-neuroendocrine prostate cancer cells, which usually express
the androgen receptor.
Possible Mechanisms of Increased Neuroendocrine
Activity in Prostate Cancer
- Increased Neuroendocrine Secretory Products
- Increased Neuroendocrine Receptors
- Decreased Neutral Endopeptidase 24.11
- Increased Peptidylglycine Alpha-amidating Monooxygenase
- Increased Prohormone Convertases
- Decreased PSA (PSA cleaves PTHrP)
Chromogranin A, as well as other neuroendocrine secretory
products, have been used as serum markers to follow the course
of the disease, particularly in androgen independent, PSA negative,
prostate cancer.
Experimental evidence suggests that neuroendocrine
factors induce proliferation and bcl-2 (an anti-apoptosis factor)
expression in adjacent non-neuroendocrine prostate cancer cells.
Neuroendocrine factors may also contribute to tumor invasiveness
and angiogenesis (VEGF is produced mainly in neuroendocrine
cells). Neuroendocrine differentiation may be an independent
prognostic factor, especially in androgen independent cancer.
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