Section of Surgery, Division of Cancer Sciences and Molecular Pathology, McGregor Building, Western Infirmary, Glasgow, UK.
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-naïve (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.
HRG expression was assessed in 2 cohorts: cohort 1 of 45 patients with paired hormone-naïve and castrate-resistant samples, and cohort 2 of 357 hormone-naïve samples. Correlations between HRG expression and biochemical relapse and survival were determined.
In cohort 1, hormone-naïve 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.
High HRG expression is associated with improved prognosis in hormone-naïve CaP and a fall in expression occurs at castration escape indicating a protective role against castrate resistance.
Grimsley SJ, Shini S, Underwood MA, Edwards J. Are you the author?
Reference: Urol Int. 2011 Aug 24. Epub ahead of print.