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Title: The identification of novel biomarkers to guide treatment in endometrial cancer
Author: Kularatne, B. Y.
ISNI:       0000 0004 7224 6712
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2017
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Endometrial cancer (EC) is the 4th commonest cancer in women in the UK. Currently histological sub-type and International Federation of Gynaecology and Obstetrics (FIGO) stage are the main determinants used in routine practice to assess a patient’s risk of recurrence after surgery, and the need for adjuvant therapies. There are currently no validated biomarkers in EC and there is an unmet need for molecular biomarkers that can accurately identify patients that are at greater risk of recurrence, and to guide treatment at relapse. In this thesis a novel biomarker panel using p53, PTEN, phospho-p70S6K, phosphostathmin, BRCA1, BRCA2, PARP1 and Rad51, has been evaluated to address this unmet clinical need. Immunohistochemistry on archived EC resection tissue has been performed using this biomarker panel and expression levels of these have been correlated to the patient’s clinico-pathological features and survival. Results demonstrate that the overexpression of p53 and phospho-stathmin and retained PTEN expression are independent predictors of overall survival (OS) and disease specific survival (DSS) in EC. Additionally, a novel liquid biopsy protocol for the identification and enumeration of circulating tumour cells (CTCs) in patients with advanced stage EC has been developed using the Parsortix device. The efficacy of this device has been compared to the Food and Drug Administration (FDA) approved CellSearch platform for enumeration of CTCs. The Parsortix device has been shown to be more efficient at enumerating CTCs and good inter-observer variability between users has been demonstrated. Further, a clinically significant cut-off level of ≥ 5 CTCs has been defined and correlated to both clinicopathological features and survival using the CellSearch platform. The expression of stathmin in CTCs (using CellSearch) has been compared to the expression of both stathmin and phospho-stathmin, in the primary tumour or biopsies taken during tumour recurrence and results have been correlated to clinico-pathological features.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available