Epidermal Growth Factor Receptor Variant III (EGFRvIII) Positivity in EGFR -Amplified Glioblastomas: Prognostic Role and Comparison between Primary and Recurrent Tumors

Approximately 40% of all glioblastomas have amplified the gene, and about half of these tumors express the EGFRvIII variant. The prognostic role of EGFRvIII in -amplified glioblastoma patients and changes in EGFRvIII expression in recurrent versus primary glioblastomas remain controversial, but such data are highly relevant for EGFRvIII-targeted therapies. -amplified glioblastomas from 106 patients were assessed for EGFRvIII positivity. Changes in amplification and EGFRvIII status from primary to recurrent glioblastomas were evaluated in 40 patients with -amplified tumors and 33 patients with -nonamplified tumors. single-nucleotide variants (SNV) were assessed in 27 patients. Data were correlated with outcome and validated in 150 glioblastoma patients from The Cancer Genome Atlas (TCGA) consortium. Sixty of 106 -amplified glioblastomas were EGFRvIII-positive (56.6%). EGFRvIII positivity was not associated with different progression-free or overall survival. EGFRvIII status was unchanged at recurrence in 35 of 40 patients with -amplified primary tumors (87.5%). Four patients lost and one patient gained EGFRvIII positivity at recurrence. None of 33 nonamplified glioblastomas acquired amplification or EGFRvIII at recurrence. SNVs were frequent in -amplified tumors, but were not linked to survival. EGFRvIII and SNVs are not prognostic in -amplified glioblastoma patients. amplification is retained in recurrent glioblastomas. Most EGFRvIII-positive glioblastomas maintain EGFRvIII positivity at recurrence. However, EGFRvIII expression may change in a subset of patients at recurrence, thus repeated biopsy with reassessment of EGFRvIII status is recommended for patients with recurrent glioblastoma to receive EGFRvIII-targeting agents. .