Combinational Analysis of FISH and Immunohistochemistry Reveals Rare Genomic Events in ALK Fusion Patterns in NSCLC that Responds to Crizotinib Treatment

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Combinational Analysis of FISH and Immunohistochemistry Reveals Rare Genomic Events in ALK Fusion Patterns in NSCLC that Responds to Crizotinib Treatment Wenbin Li, PhD, Jing Zhang, MD, Lei Guo, BS, Shannon Chuai, PhD, Ling Shan, PhD, Jianming Ying, MD, PhD Journal of Thoracic Oncology Volume 12, Issue 1, Pages 94-101 (January 2017) DOI: 10.1016/j.jtho.2016.08.145 Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Pathological and genetic features of four patients with anaplastic lymphoma kinase–positive immunohistochemistry (IHC) and an atypical and negative fluorescence in situ hybridization (FISH) result for adenocarcinoma. (A, E, I, and M) Hematoxylin and eosin staining (original magnification, ×200). (B, F, J, and O) Positive anaplastic lymphoma kinase expression (original magnification, ×200) by Ventana IHC. (C, G, K, and P) anaplastic lymphoma receptor tyrosine kinase gene (ALK) FISH analysis (original magnification, ×1000). (D, H, L, Q) Targeted next-generation sequencing of ALK gene demonstrates the BamViews of the ALK exon 20 region around the transcription breakpoint. Loci that match the reference genome are shown as gray, whereas mismatching loci are shown in different colors according to the actual genotype called (adenine, green; cytosine, blue; guanine, yellow; and thymine, red). The mismatched parts of reads come from the corresponding transcription partner genes. (A–D) One case with phosphatidylinositol binding clathrin assembly protein gene (PICALM)-ALK fusion genes demonstrated positive IHC and negative FISH patterns with fused signals. (E–H) One case with CCAAT/enhancer binding protein zeta gene (CEBPZ)-ALK fusion genes demonstrated positive IHC and atypical FISH patterns with fused signals plus isolated and attenuated 3′ ALK signals. (I–L) One case with echinoderm microtubule associated protein like 4 gene (EML4)-ALK fusion genes demonstrated positive IHC and atypical FISH patterns with fused signals plus isolated 5′ ALK signals. (M–Q) One case with EML4-ALK fusion genes demonstrated positive IHC and negative FISH patterns with fused signals. Journal of Thoracic Oncology 2017 12, 94-101DOI: (10.1016/j.jtho.2016.08.145) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions