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Molecular, genetic, patient and surgical factors involved in the development and outcome of central nervous system tumours

Kamaly-Asl, Ian

[Thesis]. Manchester, UK: The University of Manchester; 2011.

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Abstract

Prognostic factors come in a variety of forms and may be patient, tumour or environmental related.This thesis examines the interaction of prognostic factors for a variety of tumour types. It particularly focuses on single nucleotide polymorphisms (SNPs) of the vascular endothelial growth factor (VEGF) gene.The first section on meningiomas describes the frequency of sex steroid receptors in meningiomas. In this study, absence of progesterone receptors is associated with high tumour grade and male gender. Tumours that are progesterone receptor negative have an odds ratio for recurrence of 5.Choroid plexus carcinomas are aggressive malignant tumours generally occurring in young children. Gross total surgical resection has been shown to be a highly significant factor in tumour recurrence and survival. This study describes a treatment paradigm of neoadjuvant ICE chemotherapy in these children which decreases the vascularity and increase the chance of a complete removal. The operative blood loss with this regimen is reduced to 0.22 blood volumes from 1.11 blood volumes without neoadjuvant chemotherapy.The VEGF gene is highly polymorphic and SNPs of the region have previously been shown to influence VEGF protein expression. This study looks at cohorts of both adult gliomas and a variety of paediatric brain tumours; comparing them to controls. There are several associations described between the development of certain tumours and specific SNP genotypes. In addition to this, certain genotypes and haplotypes have an influence on survival of adult grade 2 astrocytomas and paediatric medulloblastomas and ependymomas. There are consistent themes to the prognostic genotypes throughout both the adult and the paediatric tumours.Prognostic factors come in a variety forms as described in this thesis. It is vital to understand the complex interaction between factors to best utilise them for the benefit of patients.