Heregulin Expression and Prognosis in Prostate Adenocarcinoma

Background: Heregulins (HRG) are a family of growth factors acting as ligands to HER3, HER4 and HER family signalling. HRG has a concentration-dependent differential growth effect - low levels mitogenic, high levels inhibitory. HRG differentially affects hormone-naive (inhibitory) and castrate-resistant (proliferative) prostate adenocarcinoma (CaP) cell lines. We postulate that differential HRG expression in CaP will be associated with alteration in tumour growth, development and prognosis. Patients and Methods: HRG expression was assessed in 2 cohorts: cohort 1 of 45 patients with paired hormone-naive and castrate-resistant samples, and cohort 2 of 357 hormone-naive samples. Correlations between HRG expression and biochemical relapse and survival were determined. Results: In cohort 1, hormone-naive samples' high membranous HRG expression was associated with increased time to relapse (p = 0.036), time to death from relapse (p = 0.002) and overall survival (p = 0.001). Membrane HRG fell significantly in post-relapse specimens. In cohort 2, high membranous HRG was associated with increased time to relapse (p = 0.004) and overall survival (p = 0.044) in patients treated with castration therapy but only with overall survival (p = 0.002) in the full cohort. Conclusion: High HRG expression is associated with improved prognosis in hormone-naive CaP and a fall in expression occurs at castration escape indicating a protective role against castrate resistance. Copyright (C) 2011 S. Karger AG, Basel