title: Immunohistochemical analysis of neuroendocrine differentiation in prostate cancer.
abstract: OBJECTIVE
  To clarify the significance of neuroendocrine differentiation in prostate cancer.
  
  
  METHODS
  We immunohistochemically examined 96 samples of prostatic cancers obtained from radical prostatectomies using a specific neuroendocrine marker and various neuropeptides, as well as markers for cell proliferation, angiogenesis and androgen-receptor expression.
  
  
  RESULTS
  We frequently found neuroendocrine cells in atrophic glands with or without chronic inflammation in nontumorous tissues. Neuroendocrine cells were detected in 36.5% of prostate cancer samples overall, but had no significant correlation to angiogenesis, cell proliferation or biochemical recurrence. However, patients with a high frequency of neuroendocrine cells (9.4%) tended to undergo preoperative hormonal therapy (p = 0.060), which led to their cancers being atrophic with inflammation. The neuroendocrine cells in these patients contained calcitonin-positive cells (p <or= 0.0001), and calcitonin positivity showed significant association with high Gleason score (p = 0.045) in the group without preoperative therapy. In the group undergoing preoperative therapy, a high prostate-specific antigen titer at first admission correlated to significant biochemical recurrence (p = 0.003).
  
  
  CONCLUSIONS
  Neuroendocrine cells may be induced under conditions of atrophy with or without chronic inflammation in both noncancerous glands and in cancers, including calcitonin-positive cells. Neither positive neuroendocrine nor positive androgen-receptor status appears predictive for biochemical recurrence.
authors.affiliation: Department of Pathology, Nara Medical University School of Medicine, Kashihara, Nara, Japan.
authors.forename: Eiwa
authors.initials: E
authors.lastname: Ishida
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Keiji
authors.initials: K
authors.lastname: Shimada
authors.forename: Masato
authors.initials: M
authors.lastname: Tasaki
authors.forename: Noboru
authors.initials: N
authors.lastname: Konishi
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002116:Calcitonin / Q000378:metabolism; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D053379:Chromogranin A / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D009490:Neurosecretory Systems / Q000378:metabolism*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C506150:CHGA protein, human; D053379:Chromogranin A; D011944:Receptors, Androgen; D002116:Calcitonin