title: Characterization of neuroendocrine differentiation in human benign prostate and prostatic adenocarcinoma.
abstract: BACKGROUND
  This report describes an immunohistopathologic analysis characterizing the incidence, pattern of distribution, and hormonal content of neuroendocrine (NE) cells in human benign prostate and prostatic adenocarcinoma.
  
  
  METHODS
  Formaldehyde-fixed, paraffin-embedded material from 15 benign prostates, 31 primary prostatic adenocarcinomas, 16 metastatic lesions, 21 primary tumors treated with short-course diethylstilbestrol (DES), and 10 specimens from hormone-refractory patients were examined. NE cells were identified using silver histochemistry and a panel of immunohistochemical NE markers (chromogranin-A, serotonin, neuron-specific enolase), and specific peptide hormone antibodies.
  
  
  RESULTS
  NE cells were identified in all benign prostates. NE cells were identified in 77% of primary untreated adenocarcinomas with no significant differences with respect to pathologic stage. NE cells were found isolated and dispersed in the tumor, composing the minority of malignant cells. Double-labeling and serial section immunohistochemistry demonstrated the coexpression of prostate-specific antigen (PSA) in NE cells. In addition to serotonin, some tumors expressed multiple hormone immunoreactivities. NE cells were identified in 56% of metastatic deposits, with a similar pattern of distribution. In DES-treated cases, NE cells were found consistently in the adjacent benign epithelium, whereas 52% of tumors contained NE cells. Hormone-refractory tumors contained NE cells in 60% of cases.
  
  
  CONCLUSIONS
  This analysis demonstrates that a significant proportion of primary and metastatic prostatic adenocarcinomas contain a subpopulation of NE cells, the expression of which does not appear to be suppressed with androgen ablation and does not correlate with pathologic stage. Furthermore, NE cells coexpress PSA, suggesting a common precursor cell of origin. The elaboration of biogenic amines and neuropeptides suggests that NE cells dispersed in prostatic carcinoma may play a paracrine growth-regulatory role.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
authors.forename: A G
authors.initials: AG
authors.lastname: Aprikian
authors.forename: C
authors.initials: C
authors.lastname: Cordon-Cardo
authors.forename: W R
authors.initials: WR
authors.lastname: Fair
authors.forename: V E
authors.initials: VE
authors.lastname: Reuter
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D001485:Basement Membrane / Q000473:pathology; D002116:Calcitonin / Q000032:analysis; D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology; D002454:Cell Differentiation; D053379:Chromogranin A; D002864:Chromogranins / Q000032:analysis; D003593:Cytoplasm / Q000648:ultrastructure; D004054:Diethylstilbestrol / Q000627:therapeutic use; D019886:Gastrin-Releasing Peptide; D005755:Gastrins / Q000032:analysis; D006801:Humans; D007633:Keratins / Q000032:analysis; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009490:Neurosecretory Systems / Q000473:pathology*; D010455:Peptides / Q000032:analysis; D011467:Prostate / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D012669:Seminal Vesicles / Q000473:pathology; D012701:Serotonin / Q000032:analysis; D013194:Staining and Labeling; D013972:Thyrotropin / Q000032:analysis
chemical_list: D053379:Chromogranin A; D002864:Chromogranins; D005755:Gastrins; D010455:Peptides; D012701:Serotonin; D007633:Keratins; D004054:Diethylstilbestrol; D019886:Gastrin-Releasing Peptide; D013972:Thyrotropin; D002116:Calcitonin; D017430:Prostate-Specific Antigen