PMID- 30796037 OWN - NLM STAT- MEDLINE DCOM- 20200706 LR - 20231107 IS - 1557-3265 (Electronic) IS - 1078-0432 (Print) IS - 1078-0432 (Linking) VI - 25 IP - 11 DP - 2019 Jun 1 TI - Comparison of Biomarker Assays for EGFR: Implications for Precision Medicine in Patients with Glioblastoma. PG - 3259-3265 LID - 10.1158/1078-0432.CCR-18-3034 [doi] AB - 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 = 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 among various methods were determined using Cohen's kappa (kappa = 0.61-0.80 defines substantial agreement) or R (2) statistics. RESULTS: EGFR mRNA expression levels by RNA sequencing (RNAseq) and RT-PCR were highly correlated with EGFR amplification assessed by FISH (kappa = 0.702). High concordance was also observed when comparing FISH to WES (kappa = 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. CI - (c)2019 American Association for Cancer Research. FAU - Lassman, Andrew B AU - Lassman AB AD - Department of Neurology & Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, New York. ABL7@cumc.columbia.edu. FAU - Roberts-Rapp, Lisa AU - Roberts-Rapp L AD - AbbVie, Inc., North Chicago, Illinois. FAU - Sokolova, Irina AU - Sokolova I AD - Abbott Molecular, Inc., Des Plaines, Illinois. FAU - Song, Minghao AU - Song M AD - Abbott Molecular, Inc., Des Plaines, Illinois. FAU - Pestova, Ekaterina AU - Pestova E AD - Abbott Molecular, Inc., Des Plaines, Illinois. FAU - Kular, Rupinder AU - Kular R AD - Abbott Molecular, Inc., Des Plaines, Illinois. FAU - Mullen, Carolyn AU - Mullen C AD - Abbott Molecular, Inc., Des Plaines, Illinois. FAU - Zha, Zheng AU - Zha Z AD - AbbVie, Inc., North Chicago, Illinois. FAU - Lu, Xin AU - Lu X AD - AbbVie, Inc., North Chicago, Illinois. FAU - Gomez, Erica AU - Gomez E AD - AbbVie, Inc., North Chicago, Illinois. FAU - Bhathena, Anahita AU - Bhathena A AD - AbbVie, Inc., North Chicago, Illinois. FAU - Maag, David AU - Maag D AD - AbbVie, Inc., North Chicago, Illinois. FAU - Kumthekar, Priya AU - Kumthekar P AD - Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. FAU - Gan, Hui K AU - Gan HK AUID- ORCID: 0000-0001-7319-8546 AD - Austin Health, Olivia Newton-John Cancer Research Institute, and La Trobe University, Melbourne, Victoria, Australia. FAU - Scott, Andrew M AU - Scott AM AD - Austin Health, Olivia Newton-John Cancer Research Institute, and La Trobe University, Melbourne, Victoria, Australia. FAU - Guseva, Maria AU - Guseva M AD - AbbVie, Inc., North Chicago, Illinois. FAU - Holen, Kyle D AU - Holen KD AD - AbbVie, Inc., North Chicago, Illinois. FAU - Ansell, Peter J AU - Ansell PJ AD - AbbVie, Inc., North Chicago, Illinois. FAU - van den Bent, Martin J AU - van den Bent MJ AUID- ORCID: 0000-0001-5710-5127 AD - Erasmus MC Cancer Center, Rotterdam, the Netherlands. LA - eng SI - ClinicalTrials.gov/NCT01800695 GR - P30 CA008748/CA/NCI NIH HHS/United States GR - P30 CA013696/CA/NCI NIH HHS/United States GR - P30 CA091842/CA/NCI NIH HHS/United States GR - UG1 CA189960/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20190222 PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (Biomarkers, Tumor) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - *Biomarkers, Tumor MH - Clinical Trials, Phase I as Topic MH - ErbB Receptors/genetics/metabolism MH - Gene Amplification MH - Gene Expression Profiling MH - Genetic Testing MH - Glioblastoma/diagnosis/*etiology/metabolism/therapy MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - *Precision Medicine/methods/standards MH - Real-Time Polymerase Chain Reaction MH - Exome Sequencing PMC - PMC8291723 MID - NIHMS1522604 EDAT- 2019/02/24 06:00 MHDA- 2020/07/07 06:00 PMCR- 2021/07/20 CRDT- 2019/02/24 06:00 PHST- 2018/09/20 00:00 [received] PHST- 2019/01/16 00:00 [revised] PHST- 2019/02/18 00:00 [accepted] PHST- 2019/02/24 06:00 [pubmed] PHST- 2020/07/07 06:00 [medline] PHST- 2019/02/24 06:00 [entrez] PHST- 2021/07/20 00:00 [pmc-release] AID - 1078-0432.CCR-18-3034 [pii] AID - 10.1158/1078-0432.CCR-18-3034 [doi] PST - ppublish SO - Clin Cancer Res. 2019 Jun 1;25(11):3259-3265. doi: 10.1158/1078-0432.CCR-18-3034. Epub 2019 Feb 22.