Detection of ALK Rearrangement by Immunohistochemistry in Lung Adenocarcinoma and the Identification of a Novel EML4-ALK Variant Ka-Fai To, MBChB, Joanna.

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Detection of ALK Rearrangement by Immunohistochemistry in Lung Adenocarcinoma and the Identification of a Novel EML4-ALK Variant Ka-Fai To, MBChB, Joanna HM Tong, PhD, King SF Yeung, BSc, Raymond WM Lung, PhD, Peggy PY Law, MPhil, Shuk Ling Chau, MPhil, Wei Kang, PhD, Carol YK Tong, MPhil, Chit Chow, PhD, Anthony WH Chan, Linda KS Leung, MBBS, Tony SK Mok, MBBS Journal of Thoracic Oncology Volume 8, Issue 7, Pages 883-891 (July 2013) DOI: 10.1097/JTO.0b013e3182904e22 Copyright © 2013 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 Representative ALK IHC images. Three cases of ALK IHC-positive cases are shown in upper panel and three negative cases are shown in lower panel. (ALK IHC, original magnification × 400). ALK, anaplastic lymphoma kinase; IHC, immunohistochemistry. Journal of Thoracic Oncology 2013 8, 883-891DOI: (10.1097/JTO.0b013e3182904e22) Copyright © 2013 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 A, ALK, IHC, FISH, and sequence electropherogram of a lung adenocarcinoma with ALK rearrangement (Ref. No. 15020). B, A representative case (Ref. No. 10946) with discordant IHC and FISH results. The tumor was positive for ALK protein expression by IHC but FISH was negative. EML4-ALK variant 1 (fusion of EML4 exon 13 and ALK exon20) was detected by reverse transcriptase-polymerase chain reaction. ALK, anaplastic lymphoma kinase; EML4, echinoderm microtubule-associated protein-like; FISH, flouresence in situ hybridization; IHC, immunohistochemistry. Journal of Thoracic Oncology 2013 8, 883-891DOI: (10.1097/JTO.0b013e3182904e22) Copyright © 2013 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3 Transforming potential of the novel EML4-ALK variant E3;ins53A20 (Ref. No. 3081). A, NIH 3T3 mouse embryo fibroblast cells were transfected with EML4-ALK variant E3;ins53A20 or empty vector. The ectopic expression of the fusion protein in NIH 3T3 cells was determined by Western blot analysis, using anti-ALK antibody. B, Nude mice were injected subcutaneously with the variant E3;ins53A20-expressing cells and mock-transfected cells on the right and left side of the dorsal flank, respectively. Tumor formation was examined after 3 weeks. C, Schematic illustration of the structure of novel EML4-ALKvariant. D, ALK Immunohistochemistry, Fluorescent in situ hybridization and sequence of the novel EML4-ALK variant E3;ins53A20. ALK, anaplastic lymphoma kinase, EML4, echinoderm microtubule-associated protein-like. Journal of Thoracic Oncology 2013 8, 883-891DOI: (10.1097/JTO.0b013e3182904e22) Copyright © 2013 International Association for the Study of Lung Cancer Terms and Conditions