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

Grimsley, Samuel John Sydney (2008) The role of EGFR, HER 2-4, heregulin and downstream signalling in prostate adenocarcinoma. MSc(R) thesis, University of Glasgow.

Abstract

Background
Currently 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 Methods
Immunohistochemical 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.

Result
High 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.

Conclusion
The 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.

• Item Type: Thesis (MSc(R))
• Qualification Level: Masters
• Keywords: Prostate Adenocarcinoma, HER, Heregulin, Immunohistochemistry, Hormone Escape
• Subjects: R Medicine > RB Pathology; R Medicine > RD Surgery
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Supervisor's Name: Edwards, Dr Joanne
• Date of Award: 2008
• Depositing User: Mr Samuel John Sydney Grimsley
• Unique ID: glathesis:2008-530
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 15 Jan 2009
• Last Modified: 10 Dec 2012 13:19
• URI: https://theses.gla.ac.uk/id/eprint/530