The role of EGFR, HER 2-4, heregulin and downstream signalling in prostate adenocarcinoma

RB Pathology;RD Surgery

Grimsley, Samuel John Sydney ; Edwards, Joanne

University:University of Glasgow

Department:Institute of Cancer Sciences

关键词: Prostate Adenocarcinoma, HER, Heregulin, Immunohistochemistry, Hormone Escape;   

Others  :  http://theses.gla.ac.uk/530/1/2008GrimsleyMSC.pdf

来源: University of Glasgow

【 摘 要 】

BackgroundCurrently evidence regarding influence of the HER tyrosine kinase family - EGFR, HER2, HER3 and HER4 - during disease progression in prostate adenocarcinoma is conflicting – both poor prognosis and no influence on outcome are reported. A small cohort pilot study of paired hormone sensitive (HSPC) and refractory (HRPC) specimens demonstrated HER2/HER4 as positively prognostic in HSPC. Heregulin (HRG), a principle HER family ligand, has previously been noted to have a differential effect on HSPC (decreased proliferation) and HRPC (increased proliferation) cell lines. This study determines influence of HER family and HRG in a larger HSPC cohort and whether influence mechanisms involve proliferation or apoptosis.Patients and MethodsImmunohistochemical staining for HRG, KI67 (proliferation), TUNEL (apoptosis) was performed on pilot study specimens. Further IHC for EGFR, HER2, HER3, HER4, HRG, KI67 and TUNEL was performed on HSPC tissue microarrays. Correlations between target protein expression and the outcomes time to biochemical relapse and overall survival were determined.ResultHigh expression of HER/HRG was correlated with improved prognosis particularly in androgen deprivation treated subcohort (e.g. high EGFR and longer time to relapse p=0.02, high HER2 and delayed relapse p=0.002, high HRG and delayed relapse-p=0.004). High expression of multiple markers increased association significance (e.g. high HER1-4 and delayed relapse p=0.001). No correlations between HER and proliferation or apoptosis were seen.ConclusionThe HER family and HRG are positively prognostic in prostate adenocarcinoma. This has implications for the use of HER family as outcome predictors to guide management.