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Title: Comparison of Biomarker Assays for EGFR: Implications for Precision Medicine in Patients with Glioblastoma.
Austin Authors: Lassman, Andrew B;Roberts-Rapp, Lisa A;Sokolova, Irina;Song, Minghao;Pestova, Ekaterina;Kular, Rupinder;Mullen, Carolyn;Zha, Zheng;Lu, Xin;Gomez, Erica;Bhathena, Anahita;Maag, David;Kumthekar, Priya;Gan, Hui K ;Scott, Andrew M ;Guseva, Maria;Holen, Kyle D;Ansell, Peter;van den Bent, Martin J
Affiliation: Neurology, Columbia University Irving Medical Center
Oncology Discovery, AbbVie Inc
Abbott Molecular, Abbott (United States)
AbbVie Inc
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Austin Health, Heidelberg, Victoria, Australia
Northwestern University Feinberg School of Medicine
La Trobe University, Melbourne, Victoria, Australia
AbbVie Laboratories
R460, AbbVie, Inc
Department of Neurology, Erasmus MC Cancer Institute
Issue Date: 1-Jun-2019 2019-02-22
Publication information: Clinical Cancer Research 2019; 25(11): 3259-3265
Abstract: Patients with glioblastoma (GBM) have a poor prognosis and are in desperate need of better therapies. As therapeutic decisions are increasingly guided by biomarkers, and EGFR abnormalities are common in GBM, thus representing a potential therapeutic target, we systematically evaluated methods of assessing EGFR amplification by multiple assays. Specifically, we evaluated correlation between fluorescence in situ hybridization (FISH), a standard assay for detecting EGFR amplification, with other methods. Formalin-fixed, paraffin-embedded tumor samples were used for all assays. EGFR amplification was detected using FISH (N = 206) and whole exome sequencing (WES, N = 74). EGFR mRNA expression was measured using reverse transcription-polymerase chain reaction (RT-PCR, N = 206) and transcriptome profiling (RNAseq, N = 64). EGFR protein expression was determined by immunohistochemistry (IHC, N = 34). Significant correlations between various methods were determined using Cohen's kappa (k = 0.61 - 0.80 defines substantial agreement) or R2 statistics. EGFR mRNA expression levels by RNAseq and RT-PCR were highly correlated with EGFR amplification assessed by FISH (k = 0.702). High concordance was also observed when comparing FISH to WES (k = 0.739). RNA expression was superior to protein expression in delineating EGFR amplification. Methods for assessing EGFR mRNA expression (RT-PCR, RNAseq) and copy number (WES), but not protein expression (IHC), can be used as surrogates for EGFR amplification (FISH) in GBM. Collectively, our results provide enhanced understanding of available screening options for patients, which may help guide EGFR-targeted therapy approaches.
DOI: 10.1158/1078-0432.CCR-18-3034
ORCID: 0000-0001-7319-8546
Journal: Clinical Cancer Research
PubMed URL: 30796037
ISSN: 1078-0432
Type: Journal Article
Appears in Collections:Journal articles

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