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

Abstract

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.