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

Abstract

BackgroundGlioblastoma is the most frequent and the most aggressive primary malignant brain tumor in adults. Standard treatment includes surgical removal of the tumor followed by concomitant chemotherapy and radiotherapy. Temozolomide, an oral alkylating agent, is currently the most commonly used chemotherapy. However, the median survival of glioblastoma multiforme (GBM) patients remains very low. Epidermal growth factor receptor variant III (EGFRvIII) is a novel marker for GBM patients of Indian origin as very few studies have been done on this molecular marker in our country. This is the first study utilizing this molecular marker among GBM patients in Rajasthan, India. This was a single institutional study that aimed to estimate the proportion of EGFRvIII mutation in GBM patients of Indian origin. MethodologyThis was a non-randomized, ambispective, single institutional observational study done on 35 brain tissue biopsies of histopathologically diagnosed and confirmed cases of GBM based on the World Health Organization 2007 Classification received in the pathology department of Dr. Sampurnanand Medical College, Jodhpur from 2015 to 2020 after applying inclusion and exclusion criteria. Molecular study of the EGFRvIII marker was conducted in all cases of GBM in the same institution on the RNA extracted from selected biopsy samples. Statistical analysis was performed using the SPSS version 22.0 software package (IBM Corp., Armonk, NY USA). The correlation between age and gender with EGFR-positive cases was analyzed, and EGFR positivity compared with previous studies. ResultsThe occurrence of the EGFRvIII mutation was found to be 17.4% (6/35 cases). The mean age of presentation of a tumor with this mutation was estimated to be 54.3 years. Males were more commonly found to be affected (66.6%, 4/6 cases). ConclusionsThus, the identification of this mutation would segregate patients who may benefit from newer therapeutic approaches. In the future, personalized treatment may be advised for GBM patients depending on the presence of the EGFRvIII mutation.

Comprehensive Molecular Genetic Analysis in Glioma Patients by Next Generation Sequencing

“…Twenty-five out of 147 tumor samples (17.0%) showed evidence of gene fusions and intragenic deletion. Intragenic deletion was identified in EGFRvIII (15/147, 10.2%), as same as previous reports [ 23 ]. This EGFRvIII was detected in the diagnosis of two subtypes of astrocytoma and glioblastoma.…”

Insights into the glioblastoma tumor microenvironment: current and emerging therapeutic approaches

“…Rindopepimut is a 14-mer peptide conjugated to the immunogenic carrier protein keyhole limpet hemocyanin (KLH) that spans the mutation site of EGFRvIII (PEPvIII: NH2-Leu-Glu-Glu-Lys-Lys-Gly-Asn-Tyr-Val-Val-Thr-Asp-His-Cyt-COOH) (Garima et al, 2022). Also known as CDX-110, it targets the EGFR deletion mutation EGFRvIII, consisting of an EGFRvIII-specific peptide conjugated to keyhole limpet hemocyanin.…”

Targeted Inhibitors of EGFR: Structure, Biology, Biomarkers, and Clinical Applications

“…EGFRvIII pathologic isoform does not contain amino acids 6-273 of wild-type EGFR, and it results in the formation of a new glycine residue at the junction site. This alteration imitates the effects of ligand binding and triggers changes in the receptor conformation by ultimately activating downstream signaling pathways [ 59 ].…”