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Title: Tumour angiogenesis in epithelial ovarian cancers
Author: Lan Fong, Wong Te Fong
ISNI:       0000 0004 2673 5742
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2007
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Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy. It is frequently diagnosed late and shows poor prognosis with a 5 year survival rate of 30%. New blood vessel formation (angiogenesis) and new lymphatic vessel growth (lymphangiogenesis) are fundamental events in tumour growth and metastatic dissemination. Despite the existence of established clinical prognostic markers for EOC, there is still a lack of clinically reliable molecular markers for assessing prognosis. In addition, little is known about the molecular events underlying EOC formation and spread. The aim of the study was to identify additional prognostic parameters in EOC and potentially pre-malignant ovarian lesions and to understand the potential mechanisms of angiogenesis / lymphangiogenesis in EOC formation. Archival paraffin wax-embedded sections, frozen tissues, serum and fluid samples of pre-malignant ovarian lesions (endometriosis, benign cystadenomas and borderline tumours) and EOC were used to assess molecular changes in EOC and these ovarian lesions compared to normal ovaries. Techniques used included immunohistochemistry, ELISA, and real-time quantitative RT-PCR which were performed to analyse molecular markers of angiogenesis and lymphangiogenesis (VEGF, VEGF-C, VEGFR-1, VEGFR-2, TP and MVD). IGF-1 isoforms involved in cell proliferation, repair and angiogenic regulation were analysed. Both VEGF and TP expression increased significantly in the formation of endometriotic and borderline lesions. VEGF-C was high in benign cystadenomas and borderline tumours. Serum VEGF levels were higher in EOC compared to premalignant benign ovarian lesions and controls, particularly in clear cell and endometrioid EOC subtypes. There was no correlation between serum VEGF and matched platelet counts. Expression of IGF-1 Ea and VEGF increased significantly from normal ovary to EOC, suggesting that VEGF may be under the regulation of IGF-lEa. This analysis has revealed the molecular interplay of angiogenic and lymphangiogenic pathways in ovarian carcinogenesis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available