ArticleThe oncologist2015
Fluorescence in situ hybridization, immunohistochemistry, and next-generation sequencing for detection of EML4-ALK rearrangement in lung cancer.
Open access · bronzeAbstract readComparative Study
In one paragraph
Article in The oncologist, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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76citing papers in PubMed, 1 pooled it
21.5field-weighted citation impact, top 1% of its field
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.
- Efficacy of D5F3 IHC for detecting ALK gene rearrangement in NSCLC patients: a systematic review and meta-analysis.Oncotarget · 2016Pooled it
- ALK ATI in solid tumours: biological evidence, diagnostic challenges, and clinical relevance. a narrative review.Molecular biology reports · 2026Review
- ALK rearrangements and resistance mutations in non-small cell lung cancer: molecular mechanisms and therapeutic implications.Cancer chemotherapy and pharmacology · 2026Review
- ALK Knock-In Reporter Reveals APE1 as a Negative Regulator ofInternational journal of molecular sciences · 2026Article
- Breaking resistance barriers: ensartinib as a milestone in anaplastic lymphoma kinase-driven non-small cell lung cancer therapy.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Evaluating the Cost of Genomic Testing for Biomarker-Driven Therapies in Oncology.Oncology and therapy · 2026Article
- Oncogenic Fusions in NSCLC: From Mechanisms to Clinical Applications.International journal of molecular sciences · 2025Review
- A Novel Intergenic Region (chr2: 30,316,870)-OncoTargets and therapy · 2024Article
- Expert consensus on the diagnosis and treatment of RET gene fusion non-small cell lung cancer in China.Thoracic cancer · 2023Article
- Detecting anaplastic lymphoma kinase (ALK) gene rearrangements with next-generation sequencing remains a reliable approach in patients with non-small-cell lung cancer.Virchows Archiv : an international journal of pathology · 2022Article
- EML4-ALK fusion gene in non-small cell lung cancer.Oncology letters · 2022Review
- Molecular diagnosis in non-small-cell lung cancer: expert opinion onJournal of clinical pathology · 2022Review
- Detection of ALK Gene Rearrangements in Non-Small Cell Lung Cancer by Immunocytochemistry and Fluorescence in Situ Hybridization on Cytologic Samples.Turk patoloji dergisi · 2022Article
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- Utilization of cytology smears improves success rates of RNA-based next-generation sequencing gene fusion assays for clinically relevant predictive biomarkers.Cancer cytopathology · 2021Article
- Copy Number Variation and Rearrangements Assessment in Cancer: Comparison of Droplet Digital PCR with the Current Approaches.International journal of molecular sciences · 2021Review
- SeekFusion - A Clinically Validated Fusion Transcript Detection Pipeline for PCR-Based Next-Generation Sequencing of RNA.Frontiers in genetics · 2021Article
- Novel MRPS9-ALK Fusion Mutation in a Lung Adenocarcinoma Patient: A Case Report.Frontiers in oncology · 2021Article
- Analysis of targeted somatic mutations in pleomorphic carcinoma of the lung using next-generation sequencing technique.Thoracic cancer · 2020Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 9 institutions in 2 countries.
Marina Pekar-ZlotinThoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, Wolfson Medical Center, Holon, Israel.
Fred R HirschThoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, Wolfson Medical Center, Holon, Israel.
Lior Soussan-GutmanThoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, Wolfson Medical Center, Holon, Israel.
Maya IlouzeThoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, Wolfson Medical Center, Holon, Israel.
Addie DvirThoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, Wolfson Medical Center, Holon, Israel.
Theresa BoyleThoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, Wolfson Medical Center, Holon, Israel.
Murry WynesThoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, Wolfson Medical Center, Holon, Israel.
Vincent A MillerThoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, Wolfson Medical Center, Holon, Israel.
Doron LipsonThoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, Wolfson Medical Center, Holon, Israel.
Gary A PalmerThoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, Wolfson Medical Center, Holon, Israel.
Siraj M AliThoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, Wolfson Medical Center, Holon, Israel.
Shlomi DekelThoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, Wolfson Medical Center, Holon, Israel.
Ronen BrennerThoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, Wolfson Medical Center, Holon, Israel.
Paul A BunnThoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, Wolfson Medical Center, Holon, Israel.
Nir PeledThoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, Wolfson Medical Center, Holon, Israel nirp@post.tau.ac.il.
Foundation Medicine (United States)Tel Aviv University · ILTeva Pharmaceuticals (Israel) · ILUniversity of Colorado Denver · USRabin Medical Center · ILSheba Medical Center · ILUniversity of Colorado Anschutz Medical Campus · USUniversity of Colorado Cancer Center · USWolfson Medical Center · IL
Funding
University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0MTissue Bank and Biomarkers CoreP50CA058187 · NCI · UNIVERSITY OF COLORADO DENVER · PI MILLER, YORK E · 1992 to 2018
$43.8MNCI NIH HHS P30 CA046934NCI NIH HHS P50 CA058187
Abstract
backgroundThe U.S. Food and Drug Administration-approved method for detecting EML4-ALK rearrangement is fluorescence in situ hybridization (FISH); however, data supporting the use of immunohistochemistry (IHC) for that purpose are accumulating. Previous studies that compared FISH and IHC considered FISH the gold standard, but none compared data with the results of next-generation sequencing (NGS) analysis. MATERIALS AND
methodsWe studied FISH and IHC (D5F3 antibody) systematically for EML4-ALK rearrangement in 51 lung adenocarcinoma patients, followed by NGS in case of discordance.
resultsOf 51 patients, 4 were positive with FISH (7.8%), and 8 were positive with IHC (15.7%). Three were positive with both. NGS confirmed that four of the five patients who were positive with IHC and negative with FISH were positive for ALK. Two were treated by crizotinib, with progression-free survival of 18 and 6 months. Considering NGS as the most accurate test, the sensitivity and specificity were 42.9% and 97.7%, respectively, for FISH and 100% and 97.7%, respectively, for IHC.
conclusionThe FISH-based method of detecting EML4-ALK rearrangement in lung cancer may miss a significant number of patients who could benefit from targeted ALK therapy. Screening for EML4-ALK rearrangement by IHC should be strongly considered, and NGS is recommended in borderline cases. Two patients who were negative with FISH and positive with IHC were treated with crizotinib and responded to therapy.
Indexed as
Gene RearrangementAdenocarcinomaAdultAgedAged, 80 and overAlgorithmsCross-Sectional StudiesDisease ProgressionFemaleHumansImmunohistochemistryIn Situ Hybridization, FluorescenceLung NeoplasmsMaleMass ScreeningMiddle AgedEML4-ALK fusion protein, humanOncogene Proteins, FusionEML4-ALKFluorescence in situ hybridizationImmunohistochemistryNext-generation sequencingNon-small cell lung cancer
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