Prognostic Significance of EGFR Gene Amplification and Overexpression in Diffuse Astrocytomas—A Literature Study

Abstract

Epidermal growth factor receptor (EGFR) has been shown to play an important role in the malignant progression of diffuse astrocytomas. Numerous studies have investigated the clinical significance of overexpression and amplification of the EGFR gene in these tumours with ambiguous results. The aim of this study was therefore to review the literature to get the current prognostic and diagnostic status. The PubMed database was used to search for papers in English in the time period 1987-2010 using the following keywords: astrocytoma, glioma, c-erbB1, EGFR, glioblastoma, HER1 and prognosis. Other inclusion criteria were: 1) studies with more than 50 patients; 2) patient age over 18 years; 3) tumour grading according to the latest World Health Organization (WHO) classification (2007) and 4) EGFR overexpression assessed by immunohistochemistry. A total of 47 publications were included and several reported positive correlations between both EGFR gene amplification and overexpression with histological malignancy grade and survival. The results are, however, encumbered with elements of uncertainty involving for instance methodological diversities and small number of patients. Larger studies with standardized procedures are necessary to fully clarify the clinical role of EGFR in human astrocytomas.

Microsomal membrane proteome of low grade diffuse astrocytomas: Differentially expressed proteins and candidate surveillance biomarkers

“…TERT promoter mutation along with wildtype IDH status has been associated with glioma prognosis and in some conditions it is implicated with alterations in chromosome 7, which harbours EGFR gene17. A survey through literature until year 201233, indicated several reports of overexpression of EGFR in Gr II tumors as has been also observed in our dataset. EGFR, and its mutant, EGFRvIII, have been also shown in exosomes and micro vesicles isolated from sera of patients with brain tumors36.…”

“…It is linked to the malignant transformation of these tumours through mutations and copy number variations as well as overexpression at RNA and protein level3334. EGFR is often used to evaluate primary GBMs35.…”

“…EGFR is often used to evaluate primary GBMs35. EGFRvIII being the most common mutation observed33, is viewed for targeted therapy for gliomas. TERT promoter mutation along with wildtype IDH status has been associated with glioma prognosis and in some conditions it is implicated with alterations in chromosome 7, which harbours EGFR gene17.…”

EGFR as a clinical marker in glioblastomas and other gliomas

“…This amplification correlated to the histological malignancy grade and lower OS (24-35). The high prevalence in grade IV tumors reflects the significant role of EGFR amplification in the molecular pathogenesis of primary and secondary GBMs (133). Poor prognosis was seen in young individuals, while more amplifications and a better prognosis were seen in older patients (24-26, 30-32, 34, 134).…”

“…Overexpression was associated with tumor grade and with PFS and OS (24, 33, 38-40, 42, 44, 49-51, 53, 56, 57). On another note, a combination of EGFR overexpression and p53 mutation was associated with a shorter survival in a population consisting of glioma patients (133).…”