Combined Use of ALK Immunohistochemistry and FISH for Optimal Detection of ALK- Rearranged Lung Adenocarcinomas Lynette M. Sholl, MD, Stanislawa Weremowicz,

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Combined Use of ALK Immunohistochemistry and FISH for Optimal Detection of ALK- Rearranged Lung Adenocarcinomas Lynette M. Sholl, MD, Stanislawa Weremowicz, PhD, Stacy W. Gray, MD, Kwok-Kin Wong, MD, PhD, Lucian R. Chirieac, MD, Neal I. Lindeman, MD, Jason L. Hornick, MD, PhD Journal of Thoracic Oncology Volume 8, Issue 3, Pages 322-328 (March 2013) DOI: 10.1097/JTO.0b013e31827db604 Copyright © 2013 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 ALK immunohistochemistry in lung ACA reveals variable levels of protein expression in ALK rearranged lung tumors. (A), Strong and diffuse reactivity (2+) and (B), heterogeneous expression ranging from absent to low (1+) in two cases with ALK rearrangement by FISH. ALK, anaplastic lymphoma kinase; FISH, fluorescence in situ hybridization; ACA, adenocarcinoma Journal of Thoracic Oncology 2013 8, 322-328DOI: (10.1097/JTO.0b013e31827db604) Copyright © 2013 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 Atypical rearrangement by FISH using the LSI ALK dual color probes (Abbott Molecular) in a patient with a coexisting EGFR L858R mutation. The tumor cells show two to three normal fused signals and an asymmetrically split green (5′ centromeric) signal with a bright single green signal (arrow) in addition to a small green signal fused to a red signal (arrowhead). ALK, anaplastic lymphoma kinase; FISH, fluorescence in situ hybridization; EGFR, epidermal growth receptor factor. Journal of Thoracic Oncology 2013 8, 322-328DOI: (10.1097/JTO.0b013e31827db604) Copyright © 2013 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3 Immunohistochemical, molecular, and cytogenetic algorithm for lung adenocarcinoma. Journal of Thoracic Oncology 2013 8, 322-328DOI: (10.1097/JTO.0b013e31827db604) Copyright © 2013 International Association for the Study of Lung Cancer Terms and Conditions