Frequency and Prognosis of Epidermal Growth Factor Receptor Variant III Mutations in Glioblastoma Multiforme among Indian Patients: A Single-Institution Study

Abstract

Background Glioblastoma multiforme (GBM) is a disease with poor outcome. Alterations or mutations in epidermal growth factor receptors (EGFRs) are found in GBM and may be targeted to improve outcomes. Aims We analyzed the frequency of EGFR variant III (vIII) mutations in patients with GBM and their outcomes after standard treatment. Materials and Methods This is a retrospective study conducted in a single tertiary cancer center in south India. Forty patients with GBM who had their entire treatment done at this center were identified, and their primary tumor tissue blocks were retrieved. Genomic DNA was extracted, and molecular analysis was performed and analyzed. The results of mutational analysis were correlated with treatment outcome of the patients. Statistical Analysis Survival outcome was analyzed using the Kaplan–Meier method. The log-rank test was used to assess the association between the groups and various parameters. Results Our study showed a similar incidence of EGFR vIII alterations as published in world literature, but we did not find any difference in overall survival (OS) and progression-free survival (PFS) in patients with EGFR vIII mutation compared with nonmutant cohort. Conclusions Contrary to the existing literature which indicated EGFR vIII alterations to be a negative prognostic indicator, our study did not find it to be an independent predictor of prognosis among Indian GBM patients treated with present standard of care.

Epidermal Growth Factor Receptor Variant III Mutation, an Emerging Molecular Marker in Glioblastoma Multiforme Patients: A Single Institution Study on the Indian Population

“…In our study, the male-to-female ratio was estimated to be 2:1 and 1.4:1 in EGFR-vIII positive cases aged ≤40 years and >40 years, respectively, while in the study of Jose et al, it was found to be 1:1 in ≤40 years and male predominance in >40 years of age, similar to the present study [28].…”

“…In this study, a total of six cases were found to be positive for the EGFRvIII mutation (17.1%), which is similar to the findings of another study that investigated 75 GBM cases and found eight cases positive for the EGFRvIII mutation (10.7%) [28]. All of these cases were aged over 40 years.…”

“…In an Indian study done by Jose et al in 2020, mutated EGFRvIII was found in 57.5% of GBM cases, which is higher than our study finding [28]. The use of different molecular techniques may be the prime reason for such variation.…”

“…The mean age of EGFRvIII-positive cases in our study was 54.3 years, while it was 56.1 ± 13.8 years in newly diagnosed GBM cases in the study by Shinojima et al [33]. The mean age of GBM cases with EGFRvIII mutation was 47.13 years in the study by Jose et al [28].…”

“…In glioblastoma, a particular group of EGFR deletions and point mutations are frequently found. These include EGFRvI (N-terminal deletion), vII (deletions of exons [14][15], vIII (deletions of exons 2-7), vIV (deletions of exons [25][26][27], and vV (deletions of exons [25][26][27][28], among which vII and vIII are oncogenic [1]. Among these mutations, EGFRvIII occurs most frequently with a global incidence of 10-50% [2].…”