The expression of HLA class I molecules and complement regulatory proteins in ovarian cancer

Rolland, Philip (2008) The expression of HLA class I molecules and complement regulatory proteins in ovarian cancer. DM thesis, University of Nottingham.

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Abstract

Over recent decades, translational ovarian cancer research has been impeded by its underappreciated molecular heterogeneity and five-year survival has remained poor. One strategy for addressing this problem is to search for molecular biomarkers that can better inform the development and targeting of novel treatments. The aim of this thesis was to construct and validate a tissue microarray of ovarian cancer cases and to survey the expression and prognostic capabilities of immunological molecular markers: specifically HLA class I and the membrane bound complement regulatory proteins CD46, CD55 and CD59. These are central to the efficacy of certain immunotherapies and while they have been shown to have prognostic power in breast and colorectal cancer, they have been investigated less in ovarian cancer.

Five copies of a tissue microarray representing 339 cases of ovarian cancer which presented to Derby City General Hospital between 1982 and 1997 were made. The array was stained for CK7, CK20, CA125, CEA, p53 and Bcl-2 following a standard immunohistochemical protocol. A linked clinical database was adapted and assessed for data consistency and subsequently used to analyse the prognostic and clinicopathological associations of the expression data. The array was then stained for HLA class I, B2microglobulin and CD59 using commercial antibodies and for CD55 and CD46 using in-house antibodies. Retained expression of HLA class I molecules independently predicted improved prognosis. High expression of CD55 and CD59 were associated with worse prognosis, though not independently of other factors. CD55 expression was more widespread than previously appreciated.

This thesis describes the discovery of a new independent marker of prognosis which suggests that immunoediting occurs in ovarian cancer, describes the distribution of markers known to have a negative impact on immunotherapy in ovarian cancer in a large series for the first time and documents the production of a valuable resource for future studies.

Item Type:Thesis (DM)
Supervisors:Spendlove, I.
Uncontrolled Keywords:Human Leukocyte Antigen, Immune editing, Immunotherapy, Tissue Microarray, TMA
Faculties/Schools:UK Campuses > Faculty of Medicine and Health Sciences > School of Molecular Medical Sciences
ID Code:600
Deposited By:Philip Rolland
Deposited On:12 Nov 2008
Last Modified:06 Feb 2009 14:44

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