Comparison of biomarker assays for EGFR: Implications for precision medicine in patients with glioblastoma

Andrew B. Lassman*, Lisa Roberts-Rapp, Irina Sokolova, Minghao Song, Ekaterina Pestova, Rupinder Kular, Carolyn Mullen, Zheng Zha, Xin Lu, Erica Gomez, Anahita Bhathena, David Maag, Priya Kumthekar, Hui K. Gan, Andrew M. Scott, Maria Guseva, Kyle D. Holen, Peter J. Ansell, Martin J. van den Bent

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

24 Citations (Scopus)

Abstract

Purpose: 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 among fluorescence in situ hybridization (FISH), a standard assay for detecting EGFR amplification, with other methods. Experimental Design: Formalin-fixed, paraffin-embedded tumor samples were used for all assays. EGFR amplification was detected using FISH (N ¼ 206) and whole-exome sequencing (WES, N ¼ 74). EGFR mRNA expression was measured using reverse transcription-polymerase chain reaction (RT-PCR, N ¼ 206) and transcriptome profiling (RNAseq, N ¼ 64). EGFR protein expression was determined by immunohistochemistry (IHC, N ¼ 34). Significant correlations among various methods were determined using Cohen's kappa (k ¼ 0.61–0.80 defines substantial agreement) or R2 statistics. Results: EGFR mRNA expression levels by RNA sequencing (RNAseq) and RT-PCR were highly correlated with EGFR amplification assessed by FISH (k ¼ 0.702). High concordance was also observed when comparing FISH to WES (k ¼ 0.739). RNA expression was superior to protein expression in delineating EGFR amplification. Conclusions: 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 therapeutic approaches.

Original languageEnglish
Pages (from-to)3259-3265
Number of pages7
JournalClinical Cancer Research
Volume25
Issue number11
DOIs
Publication statusPublished - 1 Jun 2019

Bibliographical note

Funding Information:
AbbVie, Inc. provided financial support for this study (NCT01800695) and participated in the design, study conduct, analysis and interpretation of the data, as well as the writing, review, and approval of the manuscript. All authors were involved in the data gathering, analysis, review, interpretation, and manuscript preparation and approval. The authors and AbbVie would like to thank patients and their families/caregivers; study investigators and staff; Mrinal Y. Shah, PhD for medical writing support, and Yan Sun, PhD for statistical support, both of AbbVie, Inc.; and the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine for help with genomic analysis. The Center is partially supported by NCI Cancer Center Support Grant #P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA Grant #UL1RRO24992 from the National Center for Research Resources (NCRR), a component of the NIH, and NIH Roadmap for Medical Research. A.B. Lassman was supported in part by Voices Against Brain Cancer, the William Rhodes and Louise Tilzer-Rhodes Center for Glioblastoma at NewYork-Presbyterian Hospital, and grants P30CA013696 and UG1CA189960 from the NCI.

Publisher Copyright:
© 2019 American Association for Cancer Research.

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