Evaluation of neuroendocrine staining and androgen receptor expression in incidental prostatic adenocarcinoma: prognostic implications

Urology. 2005 Oct;66(4):897-902. doi: 10.1016/j.urology.2005.04.064.


Objectives: To identify neuroendocrine cells and androgen receptors (ARs), possible predictors of cancer progression, in a series of untreated patients with incidental Stage T1a prostate cancer (PCa). Neuroendocrine cells may exert a dynamic role in the microenvironment of PCa. The AR is thought to have a central role in the propagation of prostate carcinogenesis.

Methods: Prostatectomy specimens from 81 patients with Stage T1a PCa were available for analysis. Neuroendocrine cells were detected by immunohistochemistry using antibodies to chromogranin A (CgA) and neuron-specific enolase, and the antibody against AR enabled the evaluation of the nuclear AR status. Tumor cell proliferation was assessed with the Ki-67 labeling index using MIB-1 antibody. The patients were followed up for a mean of 63.9 months, and a subsequent rise in prostate-specific antigen or positive digital rectal examination findings confirmed by biopsy was considered disease progression.

Results: Of the 81 specimens, 62 (76.54%) were positive for CgA and/or neuron-specific enolase and 19 (23.46%) were negative. A statistically significant correlation was found between CgA positivity and tumor dedifferentiation (P = 0.002). Well-differentiated tumors revealed an overexpression of ARs (P < 0.005). On multivariate analysis, worsening tumor differentiation emerged as the only independent predictor of progression-free survival (P = 0.041); however, only CgA positivity was an independent predictor of tumor progression in well and moderately differentiated tumors (P = 0.038).

Conclusions: The results of this study suggest that CgA may represent a useful marker for subsequent aggressive behavior and progression in incidental well and moderately differentiated Stage T1a PCa.

MeSH terms

  • Adenocarcinoma / chemistry*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Cell Division
  • Chromogranin A
  • Chromogranins / analysis
  • Disease-Free Survival
  • Humans
  • Incidental Findings
  • Male
  • Middle Aged
  • Neurosecretory Systems / pathology
  • Prognosis
  • Prostatic Neoplasms / chemistry*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Receptors, Androgen / analysis*
  • Receptors, Androgen / biosynthesis
  • Staining and Labeling
  • Survival Analysis


  • Biomarkers, Tumor
  • Chromogranin A
  • Chromogranins
  • Receptors, Androgen