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The effect of p53 gene mutational status, EGFR expression and proliferative potential on clinical outcome in patients with astrocytic glial tumours

Luxsuwong, Montri; (2003) The effect of p53 gene mutational status, EGFR expression and proliferative potential on clinical outcome in patients with astrocytic glial tumours. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Astrocytic tumours are common primary brain tumours in adults and display a marked propensity for malignant progression and recurrence, although the genetic mechanisms that are involved in these processes are unclear. The purpose of this study was to determine if the presence of gemistocytes, p53 mutations, Ki-67 labelling index and EGFR overexpression are associated with tumour progression and recurrence. The study was carried out in 132 patients which comprised 45 cases of grade 2 astrocytoma, 27 cases of grade 3 astrocytoma and 23 cases of grade 4 astrocytoma in which paired samples were available at the time of diagnosis and subsequently at progression. A fourth group of 37 patients with grade 4 astrocytoma without evidence of a pre-existing tumour were also examined. This latter group was divided into those patients who survived more than two years after diagnosis and those which survived less than two years after diagnosis. Alterations of p53 gene status were examined using immunocytochemical staining, PCR- SSCP analysis and sequencing. Over-expression of EGFR and the Ki-67 labelling index were determined immunocytochemically and the presence of gemistocytes determined using a morphometric approach. It was clear that tumour grade, age and Ki-67 LI were powerful independent prognostic indicators while the presence of gemistocytes, and alterations of p53 status and over-expression of EGFR were not. Patients with grade 4 tumours who survived more than 2 years tended to have higher Ki-67 LIs than those who survived less than 2 years. A novel polymorphism at codon 76 of the p53 gene was detected in about 30% of patients in this series. This polymorphism appears to be associated with those tumours that were progressive in nature or those unselected grade 4 astrocytomas in which it was possible to carry out neurosurgical debulking at recurrence. The failure to identify molecular markers other than Ki-67 LI predictive of early recurrence makes it imperative to identify new genetic markers which are associated with astrocytic tumour progression and recurrence.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: The effect of p53 gene mutational status, EGFR expression and proliferative potential on clinical outcome in patients with astrocytic glial tumours
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Health and environmental sciences; Neuropathology; Neurosurgery
URI: https://discovery.ucl.ac.uk/id/eprint/10104244
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