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Oncologist. 2015 Mar;20(3):316-22. doi: 10.1634/theoncologist.2014-0389. Epub 2015 Feb 26.

Fluorescence in situ hybridization, immunohistochemistry, and next-generation sequencing for detection of EML4-ALK rearrangement in lung cancer.

Author information

1
Thoracic 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.
2
Thoracic 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.

Abstract

BACKGROUND:

The 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 METHODS:

We studied FISH and IHC (D5F3 antibody) systematically for EML4-ALK rearrangement in 51 lung adenocarcinoma patients, followed by NGS in case of discordance.

RESULTS:

Of 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.

CONCLUSION:

The 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.

KEYWORDS:

EML4-ALK; Fluorescence in situ hybridization; Immunohistochemistry; Next-generation sequencing; Non-small cell lung cancer

PMID:
25721120
PMCID:
PMC4350802
DOI:
10.1634/theoncologist.2014-0389
[Indexed for MEDLINE]
Free PMC Article

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