The Prognostic Role of Immunohistochemical Chromogranin a Expression in Prostate Cancer Patients is Significantly Modified by Androgen-deprivation Therapy

Background: Several data suggest that neuroendocrine (NE) differentiation in prostate cancer is implicated in the development of resistance to androgen-deprivation therapy (ADT). This study was undertaken to assess the prognostic role of tissue chromogranin A (CgA) expression in patients addressed to ADT as opposed to those who did not.

Methods: Four hundred fourteen newly diagnosed prostate cancer patients, consecutively recruited in a single institution, entered the study. Two hundred fourteen patients received ADT early after diagnosis, 200 did not. Median follow-up was 85 months. CgA expression was evaluated immunohistochemically in prostate cancer needle biopsies.

Results: In multivariate analysis after adjusting for Gleason score, serum PSA, disease stage and local treatments, tissue CgA expression in overall cases was significantly associated with a shorter survival (P = 0.009) but failed to be associated with PSA progression (P = 0.10). Dividing patients according to whether they received immediate ADT or not, tissue CgA was associated with a shorter time to PSA progression in ADT-treated patients (hazard ratios (HR) 1.96, 95% confidence interval (CI): 1.37-2.81, P = 0.0001), but failed to be associated in those who did not (HR 0.87, 95% CI: 0.58-1.30, P = 0.49), interaction test P = 0.007. Conversely the survival effect of tissue CgA was not modified by ADT (interaction test, P = 0.41).

Conclusions: Tissue CgA expression, evaluated in prostate cancer needle biopsies at diagnosis, is an independent prognostic factor of survival in prostate cancer patients. The negative influence of NE differentiation on time to progression confined in ADT-treated patients suggests a role of NE differentiation in predicting endocrine resistance that deserves validation.