American Association for Cancer Research
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Supplementary Materials from Epidermal Growth Factor Receptor Variant III (EGFRvIII) Positivity in EGFR-Amplified Glioblastomas: Prognostic Role and Comparison between Primary and Recurrent Tumors

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posted on 2023-03-31, 19:20 authored by Jörg Felsberg, Bettina Hentschel, Kerstin Kaulich, Dorothee Gramatzki, Angela Zacher, Bastian Malzkorn, Marcel Kamp, Michael Sabel, Matthias Simon, Manfred Westphal, Gabriele Schackert, Jörg C. Tonn, Torsten Pietsch, Andreas von Deimling, Markus Loeffler, Guido Reifenberger, Michael Weller

Supplementary Table 1. Overview of the individual survival times, MGMT promoter methylation status and results of EGFRvIII testing by immunohistochemistry (IHC) or reverse transcription-PCR (RT-PCR) in primary tumors (PT) and recurrent tumors (RT) of 106 patients with newly diagnosed EGFR-amplified glioblastomas, IDH-wildtype. PFS, progression-free survival; OS, overall survival; n.d., not determined; * deceased patients; ** no progression documented; {section sign} excluded for Kaplan-Meier analyses because EGFRvIII was determined at second recurrence. Supplementary Table 2. Overview of individual survival times, MGMT promoter methylation status and results of EGFRvIII testing by immunohistochemistry (IHC) or reverse transcription-PCR (RT-PCR) in primary tumors (PT) and recurrent tumors (RT) of 33 patients with newly diagnosed IDH-wildtype, EGFR-non-amplified glioblastomas. N.d., not determined. * Deceased patients. Supplementary Table 3. Overview of the EGFR single nucleotide variants (SNVs) detected by next generation sequencing (NGS) in primary (PT) and recurrent (RT) glioblastomas of 27 patients. Mutant allele frequencies in percent are provided for each single nucleotide variant (SNV). Supplementary Table 4. Overview of the validation cohort of 150 TCGA patients with IDH-wildtype glioblastoma (GBM). Supplementary Figure 1. Demonstration of regional heterogeneity of EGFRvIII expression in an EGFR-amplified primary glioblastoma, IDH-wildtype (patient 96). Supplementary Figure 2. EGFRvIII expression and MGMT promoter methylation status and survival outcome in 77 patients with EGFR-amplified glioblastomas treated with radiotherapy and temozolomide chemotherapy. Supplementary Figure 3. Survival of patients with EGFR-amplified glioblastomas, IDH-wildtype, according to the EGFRvIII status in the subgroups of patients who received second surgery (52 patients) or did not receive second surgery (54 patients). Supplementary Figure 4. Survival of 27 German Glioma Network (GGN) patients with glioblastoma, IDH-wildtype, according to presence (9 patients) or absence (18 patients) of at least one EGFR single nucleotide variant (SNV) as detected by NGS of the EGFR coding sequence. Supplementary Figure 5. Survival of TCGA patients with glioblastoma, IDH-wildtype, according to EGFR amplification, presence of at least one EGFR single nucleotide variant (SNV), and EGFRvIII positivity.

Funding

German Cancer Aid

Merck, EMD, Darmstadt, Germany

German Cancer Consortium

Heinrich Heine University Düsseldorf

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ARTICLE ABSTRACT

Purpose: Approximately 40% of all glioblastomas have amplified the EGFR gene, and about half of these tumors express the EGFRvIII variant. The prognostic role of EGFRvIII in EGFR-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.Experimental Design: EGFR-amplified glioblastomas from 106 patients were assessed for EGFRvIII positivity. Changes in EGFR amplification and EGFRvIII status from primary to recurrent glioblastomas were evaluated in 40 patients with EGFR-amplified tumors and 33 patients with EGFR–nonamplified tumors. EGFR 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.Results: Sixty of 106 EGFR-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 EGFR-amplified primary tumors (87.5%). Four patients lost and one patient gained EGFRvIII positivity at recurrence. None of 33 EGFR-nonamplified glioblastomas acquired EGFR amplification or EGFRvIII at recurrence. EGFR SNVs were frequent in EGFR-amplified tumors, but were not linked to survival.Conclusions: EGFRvIII and EGFR SNVs are not prognostic in EGFR-amplified glioblastoma patients. EGFR 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. Clin Cancer Res; 23(22); 6846–55. ©2017 AACR.

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