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Fluorescence in Situ Hybridization (FISH) for Detecting Anaplastic Lymphoma Kinase (ALK) Rearrangement in Lung Cancer: Clinically Relevant Technical Aspects

1
Department of Hematopathogy/Clinical Cytogenetics Laboratory, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
2
Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(16), 3939; https://doi.org/10.3390/ijms20163939
Received: 30 June 2019 / Revised: 8 August 2019 / Accepted: 11 August 2019 / Published: 13 August 2019
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Abstract

In 2011, the Vysis Break Apart ALK fluorescence in situ hybridization (FISH) assay was approved by the United States Food and Drug Administration as a companion diagnostic for detecting ALK rearrangement in lung cancer patients who may benefit from treatment of tyrosine kinase inhibitor therapy. This assay is the current “gold standard”. According to updated ALK testing guidelines from the College of American Pathologists, the International Association for the Study of Lung Cancer and the Association for Molecular Pathology published in 2018, ALK immunohistochemistry is formally an alternative to ALK FISH, and simultaneous detection of multiple hot spots, including, at least, ALK, ROS1, RET, MET, ERBB2, BRAF and KRAS genes is also recommended while performing next generation sequencing (NGS)-based testing. Therefore, ALK status in a specimen can be tested by different methods and platforms, even in the same institution or laboratory. In this review, we discuss several clinically relevant technical aspects of ALK FISH, including pros and cons of the unique two-step (50- to 100-cell) analysis approach employed in the Vysis Break Apart ALK FISH assay, including: the preset cutoff value of ≥15% for a positive result; technical aspects and biology of discordant results obtained by different methods; and incidental findings, such as ALK copy number gain or amplification and co-existent driver mutations. These issues have practical implications for ALK testing in the clinical laboratory following the updated guidelines. View Full-Text
Keywords: ALK; fluorescence in situ hybridization (FISH); immunohistochemistry (IHC); next generation sequencing (NGS); cutoff value; discordant result; incidental finding ALK; fluorescence in situ hybridization (FISH); immunohistochemistry (IHC); next generation sequencing (NGS); cutoff value; discordant result; incidental finding
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Tang, Z.; Wang, L.; Tang, G.; Medeiros, L.J. Fluorescence in Situ Hybridization (FISH) for Detecting Anaplastic Lymphoma Kinase (ALK) Rearrangement in Lung Cancer: Clinically Relevant Technical Aspects. Int. J. Mol. Sci. 2019, 20, 3939.

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