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dc.contributor.authorHo-Yen, Colan Maxwell
dc.date.accessioned2015-09-28T11:54:36Z
dc.date.available2015-09-28T11:54:36Z
dc.date.issued2014-05
dc.identifier.citationHo-Yen, C. 2014. The Significance of C-Met in Different Molecular Sub-Types of Invasive Breast Cancer. Queen Mary University of London.en_US
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/8907
dc.descriptionPhDen_US
dc.description.abstractIntroduction: Basal-like (BL) breast cancer is an aggressive sub-type of breast cancer for which there is no targeted systemic therapy. C-Met is a receptor tyrosine kinase implicated in breast cancer. Clinical trials assessing the efficacy of anti-c-Met therapy are underway, yet few studies have analysed the clinical significance of c-Met expression and/or activation in breast cancer, in particular whether there is a correlation with molecular sub-type. The aims of this study are: 1) to establish the clinical significance of c-Met expression in invasive breast cancer, 2) evaluate the novel proximity ligation assay (PLA) as a method of measuring c-Met activation and 3) address the effect of hepatocyte growth factor (HGF)-mediated c-Met phosphorylation on migration and protein expression in cell lines representative of the BL sub-type. Methods: Immunohistochemistry for c-Met was performed on 1455 cases of breast cancer using tissue microarray (TMA) technology. The PLA was performed on TMAs constructed from 181 breast cancers. C-Met expression and the PLA product were correlated with clinico-pathological parameters and survival. The effects of HGF on cell migration and protein expression were assessed using migration assays, western blots and immunofluorescent studies. Results: C-Met expression was independently associated with BL breast cancer (odds ratio = 6.44, 95% confidence interval (CI) = 1.74-23.78, p = 0.005) and reduced overall survival (hazard ratio = 1.81, 95% CI = 1.07-3.06), p = 0.026). The PLA signal was not associated with molecular sub-type or survival. HGF stimulation was associated with a significant increase in BL cell migration (p < 0.01) but no evidence of epithelial-mesenchymal transition was observed. Conclusion: My findings suggest BL breast cancer patients should be included in future trials of anti-c-Met therapy. Further work is necessary to establish the prognostic utility of the PLA as a measure of c-Met activation and the mechanisms driving HGF-mediated cell migration.en_US
dc.description.sponsorshipCancer Research UKen_US
dc.language.isoenen_US
dc.publisherQueen Mary University of Londonen_US
dc.relationThe copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author
dc.subjectMedicineen_US
dc.subjectBreast canceren_US
dc.subjectBasal-like breast canceren_US
dc.subjectc-Meten_US
dc.titleThe Significance of C-Met in Different Molecular Sub-Types of Invasive Breast Cancer.en_US
dc.typeThesisen_US


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