Genetic Alterations of Epidermal Growth Factor Receptor in Glioblastoma: The Usefulness of Immunohistochemistry

Epidermal growth factor receptor (EGFR) amplification is one of the common alterations in IDH-wildtype glioblastoma. It is frequently associated with EGFRvIII mutation. To evaluate the correlation between EGFR overexpression, gene amplification, and EGFRvIII mutation, we performed immunohistochemical (IHC) analysis, fluorescence in situ hybridization by Vysis LSI EGFR/CEP7 dual color probe, and polymerase chain reaction studies in 76 patients diagnosed with glioblastomas (67 IDH-wildtype and 9 IDH-mutant). EGFR expression was scored ranging from 0 to 3+. Using formalin-fixed paraffin-embedded sections, real-time reverse transcription-polymerase chain reaction was carried out with primers specific for EGFRvIII and EGFR wildtype. In addition, we evaluated the impact of EGFR status on prognosis. EGFR gene amplifications and EGFRvIII mutations were identified in 30.3% and 15.5% of all cases, respectively. All the EGFR-amplified or EGFRvIII mutant cases were IDH-wildtype glioblastomas and tested positive with IHC. The sensitivity and specificity of EGFR IHC predicting EGFR gene amplification status were 100.0% and 46.5%, respectively. The EGFR-amplified cases tended to show more intense immunostaining (3+) in a considerable number of tumor cells (>= 50%). Survival analyses of 37 IDH-wildtype glioblastoma patients revealed that none of the EGFR alterations significantly affected prognosis. EGFR IHC displayed high sensitivity and low specificity in predicting EGFR gene amplification, and interpretation of IHC results is a challenge. Therefore, EGFR IHC represents a possible screening tool for evaluation of EGFR gene amplification in clinical neuropathology, and both the intensity and proportion score facilitate interpretation of EGFR IHC.