The prognostic significance of loss of the androgen receptor and neuroendocrine differentiation in prostate biopsy specimens among castration-resistant prostate cancer patients.

Prostate cancer (PCa) is a leading cause of mortality, and despite good response to androgen ablation this response is eventually lost. In the present study, androgen receptor (AR) expression and neuroendocrine differentiation (NED) were evaluated in hormone-sensitive (HSPC) and castration-resistant prostate cancers (CRPC). Prostate tissues were obtained from 20 HSPC patients at diagnosis and 28 CRPC patients at castration-resistant progression. AR, chromogranin A (CGA) and neuron-specific enolase (NSE) were evaluated by immunohistochemical staining (IHS) in representative positive cores for PCa. IHS intensity was graded as negative, 0; positive, 1+ and strongly positive, 2+. The proportion of the 1+ and 2+ areas in PCa cells was determined. PCa was considered to be in NED if ≥50% of the tumor cells were 1+ or 2+ for CGA or NSE. The observed IHS intensity (0/1+/2+) for AR, CGA and NSE was 0/4/16, 5/11/4 and 11/4/5 in HSPC patients and 9/3/16, 5/8/15 and 8/4/16 in CRPC patients, respectively. AR expression was positive in all the HSPC and 19/28 CRPC patients (P=0.0049). NED was observed in 9/20 HSPC and 20/28 CRPC patients (P=0.0649). NED was significantly associated with a negative AR expression in CRPC patients (P=0.0292). Multivariate analysis revealed that age, AR expression and strong NED were independent parameters for prognosis following castration-resistant progression. In conclusion, prostate biopsy following castration-resistant progression was necessary. AR was lost in a subset of CRPC. NED was observed more frequently in CRPC vs. HSPC and was associated with a worse prognosis.