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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.

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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 > Institute 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: http://theses.gla.ac.uk/id/eprint/530

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