Bright-Field Dual-Color Chromogenic In Situ Hybridization for Diagnosing Echinoderm Microtubule-Associated Protein-Like 4-Anaplastic Lymphoma Kinase-Positive.

Slides:



Advertisements
Similar presentations
Hippo Pathway Gene Mutations in Malignant Mesothelioma: Revealed by RNA and Targeted Exon Sequencing Akihiko Miyanaga, MD, PhD, Mari Masuda, PhD, Koji.
Advertisements

Naomi Fujioka, MD, Christopher A. French, MD, Michael J
Droplet Digital PCR for Absolute Quantification of EML4-ALK Gene Rearrangement in Lung Adenocarcinoma  Qiushi Wang, Xin Yang, Yong He, Qiang Ma, Li Lin,
Detection of ALK Gene Rearrangement in Non-small Cell Lung Cancer: A Comparison of Fluorescence In Situ Hybridization and Chromogenic In Situ Hybridization.
New Methods for ALK Status Diagnosis in Non–Small-Cell Lung Cancer: An Improved ALK Immunohistochemical Assay and a New, Brightfield, Dual ALK IHC–In.
Detection of Rearrangements and Transcriptional Up-Regulation of ALK in FFPE Lung Cancer Specimens Using a Novel, Sensitive, Quantitative Reverse Transcription.
Next-Generation Sequencing Identifies and Immunohistochemistry Confirms a Novel Crizotinib-Sensitive ALK Rearrangement in a Patient with Metastatic Non–Small-Cell.
ALK FISH and IHC: You Cannot Have One without the Other
Heterogeneity of Anaplastic Lymphoma Kinase Gene Rearrangement in Non–Small-Cell Lung Carcinomas: A Comparative Study Between Small Biopsy and Excision.
Jessica J. Lin, MD, Lauren L. Ritterhouse, MD, PhD, Siraj M
Transformation to Sarcomatoid Carcinoma in ALK-Rearranged Adenocarcinoma, Which Developed Acquired Resistance to Crizotinib and Received Subsequent Chemotherapies 
Treatment of Lung Cancer with an ALK Inhibitor After EML4-ALK Fusion Gene Detection Using Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration 
Characterization of Fibroblast Growth Factor Receptor 1 in Small-Cell Lung Cancer  Anish Thomas, MD, Jih-Hsiang Lee, MD, Zied Abdullaev, PhD, Kang-Seo.
FISH Analysis of Crizotinib Target Genes ROS1/ALK/MET in Malignant Mesothelioma  Sandra Salvi, PhD, Serena Varesano, PhD, Simona Boccardo, PhD, Jean Louis.
Clinicopathologic Analysis of ROS1-Rearranged Non–Small-Cell Lung Cancer and Proposal of a Diagnostic Algorithm  Heounjeong Go, MD, PhD, Dong-Wan Kim,
A Sensitive ALK Immunohistochemistry Companion Diagnostic Test Identifies Patients Eligible for Treatment with Crizotinib  Trish Thorne-Nuzzo, BS, Crystal.
Large-Scale Screening and Molecular Characterization of EML4-ALK Fusion Variants in Archival Non–Small-Cell Lung Cancer Tumor Specimens Using Quantitative.
Increased ALK Gene Copy Number and Amplification are Frequent in Non-small Cell Lung Cancer  Marta Salido, MSc, Lara Pijuan, MD, PhD, Luz Martínez-Avilés,
Loss of Phosphatase and Tensin Homolog Protein Expression Is an Independent Poor Prognostic Marker in Lung Adenocarcinoma  Naoki Yanagawa, MD, PhD, Charles.
MET and EGFR Mutations Identified in ALK-Rearranged Pulmonary Adenocarcinoma: Molecular Analysis of 25 ALK-Positive Cases  Jennifer M. Boland, MD, Jin.
Interpretation of Anti-ALK Immunohistochemistry Results
High-Dose Crizotinib for Brain Metastases Refractory to Standard-Dose Crizotinib  Young Hak Kim, MD, Hiroaki Ozasa, MD, Hiroki Nagai, MD, Yuichi Sakamori,
Custom Gene Capture and Next-Generation Sequencing to Resolve Discordant ALK Status by FISH and IHC in Lung Adenocarcinoma  Jin Sung Jang, Xiaoke Wang,
A Case of Large-Cell Neuroendocrine Carcinoma Harboring an EML4–ALK Rearrangement with Resistance to the ALK Inhibitor Crizotinib  Naoki Omachi, MD, Shigeki.
A Case of Lung Adenocarcinoma Resistant to Crizotinib Harboring a Novel EML4-ALK Variant, Exon 6 of EML4 Fused to Exon 18 of ALK  Satoshi Anai, MD, Masafumi.
Comprehensive Hybrid Capture–Based Next-Generation Sequencing Identifies a Double ALK Gene Fusion in a Patient Previously Identified to Be False-Negative.
ALK and NRG1 Fusions Coexist in a Patient with Signet Ring Cell Lung Adenocarcinoma  Lucia Anna Muscarella, PhD, Domenico Trombetta, PhD, Federico Pio.
A Case of Squamous Cell Carcinoma Harboring an EML4-ALK Rearrangement that Was Unsuccessfully Treated with the ALK Inhibitor Alectinib  Akihiro Tamiya,
Dual IHC and FISH Testing for ALK Gene Rearrangement in Lung Adenocarcinomas in a Routine Practice: A French Study  Anne McLeer-Florin, PhD, Denis Moro-Sibilot,
Combined Use of ALK Immunohistochemistry and FISH for Optimal Detection of ALK- Rearranged Lung Adenocarcinomas  Lynette M. Sholl, MD, Stanislawa Weremowicz,
ALK/EML4 Fusion Gene May Be Found in Pure Squamous Carcinoma of the Lung  Anna Caliò, MD, Alessia Nottegar, MD, Eliana Gilioli, MD, Emilio Bria, MD, Sara.
A Sensitive ALK Immunohistochemistry Companion Diagnostic Test Identifies Patients Eligible for Treatment with Crizotinib  Trish Thorne-Nuzzo, BS, Crystal.
Combinational Analysis of FISH and Immunohistochemistry Reveals Rare Genomic Events in ALK Fusion Patterns in NSCLC that Responds to Crizotinib Treatment 
Reliability Assurance of Detection of EML4-ALK Rearrangement in Non–Small Cell Lung Cancer: The Results of Proficiency Testing in China  Yulong Li, MD,
ALK Rearrangement Detected in a Focus of Pulmonary Atypical Adenomatous Hyperplasia  Filippo Lococo, MD, Alessandra Bisagni, MD, Maria Cecilia Mengoli,
Searching for ROS1 Rearrangements in Lung Cancer by Fluorescent In Situ Hybridization: The Importance of Probe Design  Arnaud Uguen, MD, Pascale Marcorelles,
A Novel EML4-ALK Variant: Exon 6 of EML4 Fused to Exon 19 of ALK
Assessment of ALK Status by FISH on 1000 Spanish Non-Small Cell Lung Cancer Patients  Joana Vidal, MD, Sergi Clavé, MSc, Silvia de Muga, PhD, Iria González,
Parallel FISH and Immunohistochemical Studies of ALK Status in 3244 Non–Small-Cell Lung Cancers Reveal Major Discordances  Florian Cabillic, PharMD, PhD,
Detection of ALK Rearrangement by Immunohistochemistry in Lung Adenocarcinoma and the Identification of a Novel EML4-ALK Variant  Ka-Fai To, MBChB, Joanna.
ALK Testing in Lung Adenocarcinoma: Technical Aspects to Improve FISH Evaluation in Daily Practice  Vittoria Martin, PhD, Barbara Bernasconi, PhD, Elisabetta.
A Comprehensive Analysis of p16 Expression, Gene Status, and Promoter Hypermethylation In Surgically Resected Non-small Cell Lung Carcinomas  William.
First Case of Combined Small-Cell Lung Cancer with Adenocarcinoma Harboring EML4- ALK Fusion and an Exon 19 EGFR Mutation in Each Histological Component 
Response to Crizotinib Observed in Lung Adenocarcinoma with MET Copy Number Gain but without a High-Level MET/CEP7 Ratio, MET Overexpression, or Exon.
Erratum Journal of Thoracic Oncology
NUT Rearrangement is Uncommon in Human Thymic Epithelial Tumors
Arnaud Uguen, MD, PhD  Journal of Thoracic Oncology 
A Case of ALK-Rearranged Adenocarcinoma with Small Cell Carcinoma-Like Transformation and Resistance to Crizotinib  Yoon Jin Cha, MD, PhD, Byoung Chul.
High MET Receptor Expression But Not Gene Amplification in ALK 2p23 Rearrangement Positive Non–Small-Cell Lung Cancer  Yan Feng, MD, Eugen C. Minca, MD,
A Novel Mechanism of EML4-ALK Rearrangement Mediated by Chromothripsis in a Patient-Derived Cell Line  Tatsushi Kodama, MS, Noriko Motoi, MD, PhD, Hironori.
Detection of ALK-Positive Non–Small-Cell Lung Cancers on Cytological Specimens: High Accuracy of Immunocytochemistry with the 5A4 Clone  Spasenija Savic,
Multiplex Diagnosis of Oncogenic Fusion and MET Exon Skipping by Molecular Counting Using Formalin-Fixed Paraffin Embedded Lung Adenocarcinoma Tissues 
Clinicopathologic Characteristics and Outcomes of Patients with Anaplastic Lymphoma Kinase-Positive Advanced Pulmonary Adenocarcinoma: Suggestion for.
Histological Scoring for Small Lung Adenocarcinomas 2 cm or Less in Diameter: A Reliable Prognostic Indicator  Akiko Miyagi Maeshima, MD, Naobumi Tochigi,
Daniel B. Costa, MD, PhD, Susumu Kobayashi, MD, PhD 
Frequent BRAF or EGFR Mutations in Ciliated Muconodular Papillary Tumors of the Lung  Tsugumasa Kamata, MD, Kuniko Sunami, MD, Akihiko Yoshida, MD, PhD,
Lung Adenocarcinoma with Concurrent Exon 19 EGFR Mutation and ALK Rearrangement Responding to Erlotinib  Sanjay Popat, MRCP, PhD, Alexandra Vieira de.
Atypical Negative ALK Break-Apart FISH Harboring a Crizotinib-Responsive ALK Rearrangement in Non–Small-Cell Lung Cancer  Shengxiang Ren, MD, PhD, Fred.
A Novel Fusion of TPR and ALK in Lung Adenocarcinoma
C-MET/Phospho-MET Protein Expression and MET Gene Copy Number in Non-small Cell Lung Carcinomas  Koji Tsuta, MD, PhD, Yoshiki Kozu, MD, PhD, Takahiro.
Toni-Maree Rogers, BMLS, Prudence A
Immunohistochemistry is a Reliable Screening Tool for Identification of ALK Rearrangement in Non–Small-Cell Lung Carcinoma and is Antibody Dependent 
BIRC6-ALK, a Novel Fusion Gene in ALK Break-Apart FISH-Negative Lung Adenocarcinoma, Responds to Crizotinib  Ling Shan, PhD, Peidi Jiang, MD, Feng Xu,
Concomitant Epidermal Growth Factor Receptor Mutation and EML4-ALK Fusion in a Patient with Multifocal Lung Adenocarcinomas  Jun Fan, MD  Journal of Thoracic.
Clinical Implications of Variant ALK FISH Rearrangement Patterns
Good Response to Gefitinib in Lung Adenocarcinoma Harboring Coexisting EML4-ALK Fusion Gene and EGFR Mutation  Yao-Wen Kuo, MD, Shang-Gin Wu, MD, Chao-Chi.
An International Interpretation Study Using the ALK IHC Antibody D5F3 and a Sensitive Detection Kit Demonstrates High Concordance between ALK IHC and.
A Dramatic Response to Crizotinib in a Non–Small-Cell Lung Cancer Patient with IHC- Positive and FISH-Negative ALK  Jong-Mu Sun, MD, PhD, Yoon-La Choi,
ALK Status Testing in Non–Small-Cell Lung Carcinoma by FISH on ThinPrep Slides with Cytology Material  Eugen C. Minca, MD, PhD, Christopher P. Lanigan,
ALK Gene Rearrangements: A New Therapeutic Target in a Molecularly Defined Subset of Non-small Cell Lung Cancer  Benjamin Solomon, MBBS, PhD, Marileila.
Presentation transcript:

Bright-Field Dual-Color Chromogenic In Situ Hybridization for Diagnosing Echinoderm Microtubule-Associated Protein-Like 4-Anaplastic Lymphoma Kinase-Positive Lung Adenocarcinomas  Akihiko Yoshida, MD, Koji Tsuta, MD, PhD, Hiroaki Nitta, PhD, Yutaka Hatanaka, PhD, Hisao Asamura, MD, Ikuo Sekine, MD, PhD, Thomas M. Grogan, MD, Masashi Fukayama, MD, PhD, Tatsuhiro Shibata, MD, PhD, Koh Furuta, MD, PhD, Takashi Kohno, PhD, Hitoshi Tsuda, MD, PhD  Journal of Thoracic Oncology  Volume 6, Issue 10, Pages 1677-1686 (October 2011) DOI: 10.1097/JTO.0b013e3182286d25 Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 Schematic design of the break-apart probe set for anaplastic large cell lymphoma (ALK) gene. ALK break-apart probe set was designed to hybridize with the neighboring centromeric (5′ probe labeled with digoxigenin) and telomeric (3′ probe labeled with 2,4 dinitrophenyl) sequence of ALK gene. Journal of Thoracic Oncology 2011 6, 1677-1686DOI: (10.1097/JTO.0b013e3182286d25) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 Anaplastic lymphoma kinase (ALK) break-apart chromogenic in situ hybridization (CISH) signals were categorized into the following seven patterns. Blue signal represents 5′ region to ALK, and red signal represents 3′ to ALK. A, fused 3′/5′ only; (B) fused 3′/5′ and split; (C) split only; (D) fused 3′/5′ and isolated 5′; (E) fused 3′/5′ and isolated 3′; (F) isolated 5′ only; and (G) isolated 3′ only (ALK-break-apart CISH, ×1000). Journal of Thoracic Oncology 2011 6, 1677-1686DOI: (10.1097/JTO.0b013e3182286d25) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3 A, The results of an anaplastic lymphoma kinase (ALK) break-apart chromogenic in situ hybridization assay represented as a bar chart. Yellow, red, blue, and gray areas represent the percentages of tumor cells with split signals (fused and split signals or just split signals), isolated 3′ signals (fused and red signals or just red signals), isolated 5′ signals (fused and blue signals or just blue signals), and only fused signals, respectively. A combination of the yellow and red areas shows the rate of rearrangement-positive cells. B, The results of an ALK break-apart fluorescence in situ hybridization assay represented as a bar chart. Yellow, orange, green, and gray areas represent the percentages of tumor cells with split signals (fused and split signals or just split signals), isolated 3′ signals (fused and orange signals or just orange signals), isolated 5′ signals (fused and green signals or just green signals), and only fused signals, respectively. A combination of the yellow and orange areas shows the rate of rearrangement-positive rate. Journal of Thoracic Oncology 2011 6, 1677-1686DOI: (10.1097/JTO.0b013e3182286d25) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 4 A, anaplastic lymphoma kinase (ALK) break-apart chromogenic in situ hybridization in an echinoderm microtubule-associated protein-like 4 (EML4)-ALK-positive lung adenocarcinoma (P1) displayed a significant number of rearrangement signals (arrows, split and lone 3′ signals, ALK-break-apart CISH, ×600). B, EML4-ALK-negative carcinoma (N1) predominantly showed 3′/5′ fused signals that looked purple or black due to colocalization of red and blue signals (ALK-break-apart CISH, ×600). Journal of Thoracic Oncology 2011 6, 1677-1686DOI: (10.1097/JTO.0b013e3182286d25) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 5 A, The only CISH false-negative case (P4) harbored a large number of cells displaying isolated 5′ signals unaccompanied by 3′ signals (ALK-break-apart CISH, ×1000). B, This atypical profile was replicated by fluorescence in situ hybridization (FISH) as predominantly lone 5′ green signal pattern (ALK-break-apart FISH, ×1000). Journal of Thoracic Oncology 2011 6, 1677-1686DOI: (10.1097/JTO.0b013e3182286d25) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 6 Anaplastic lymphoma kinase (ALK) immunohistochemistry diffusely stained all the echinoderm microtubule-associated protein-like 4 (EML4)-ALK-positive lung adenocarcinomas, and it was negative in all the EML4-ALK-negative cases (A, negative; B, weakly positive; C, moderately positive; and D, strongly positive. ALK immunohistochemistry, ×200). Journal of Thoracic Oncology 2011 6, 1677-1686DOI: (10.1097/JTO.0b013e3182286d25) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions