Heterogeneity of EGFR Aberrations and Correlation with Histological Structures: Analyses of Therapy-Naive Isogenic Lung Cancer Lesions with EGFR Mutation

Slides:

Advertisements

Similar presentations

Frances A Shepherd, MD, Rafael Rosell, MD Journal of Thoracic Oncology

Advertisements

Clinicopathologic Characteristics of the EGFR Gene Mutation in Non–small Cell Lung Cancer Anne S. Tsao, MD, Xi Ming Tang, MD, PhD, Bradley Sabloff, MD,

Adi F. Gazdar, MD, Fred R. Hirsch, MD, PhD, John D. Minna, MD

Carcinoma NOS is a Common Histologic Diagnosis and is Increasing in Proportion Among Non-small Cell Lung Cancer Histologies Sai-Hong Ignatius Ou, MD,

EGFR-GRB2 Protein Colocalization Is a Prognostic Factor Unrelated to Overall EGFR Expression or EGFR Mutation in Lung Adenocarcinoma Maria I. Toki, MD,

Detection of ALK Gene Rearrangement in Non-small Cell Lung Cancer: A Comparison of Fluorescence In Situ Hybridization and Chromogenic In Situ Hybridization.

Malignant Pleural Mesothelioma Harboring Both G719C and S768I Mutations of EGFR Successfully Treated with Afatinib Nobukazu Agatsuma, MD Journal of.

EGFR Status in Mesothelioma: Possible Implications for the Efficacy of Anti-EGFR and Anti-MET Therapies Sandra Salvi, PhD, Serena Varesano, PhD, Simona.

Molecular Predictors of Sensitivity to the MET Inhibitor PHA in Lung Carcinoma Cells Daisuke Matsubara, MD, PhD, Shumpei Ishikawa, MD, PhD, Sachiko.

Malignant Pleural Mesothelioma Harboring Both G719C and S768I Mutations of EGFR Successfully Treated with Afatinib Nobukazu Agatsuma, MD Journal of.

Comparison of 22C3 PD-L1 Expression between Surgically Resected Specimens and Paired Tissue Microarrays in Non–Small Cell Lung Cancer Chao Li, MD, PhD,

A Case of Concurrent De Novo C797S and L858R EGFR Mutation Detected in Stage IA Non–Small Cell Lung Cancer Patient Jong Sik Lee, MD, Jae Young Hur, PhD,

Adi F. Gazdar, MD, Fred R. Hirsch, MD, PhD, John D. Minna, MD

Clinicopathologic Analysis of ROS1-Rearranged Non–Small-Cell Lung Cancer and Proposal of a Diagnostic Algorithm Heounjeong Go, MD, PhD, Dong-Wan Kim,

Differential Diagnosis of Primary Versus Metastatic Pulmonary Adenocarcinomas Using Gene Mutation Analyses: A Case Report Yoshimasa Nakazato, MD, Ryota.

A Sensitive ALK Immunohistochemistry Companion Diagnostic Test Identifies Patients Eligible for Treatment with Crizotinib Trish Thorne-Nuzzo, BS, Crystal.

Heterogeneity in Immune Marker Expression after Acquisition of Resistance to EGFR Kinase Inhibitors: Analysis of a Case with Small Cell Lung Cancer Transformation

Association of Epidermal Growth Factor Receptor Activating Mutations with Low ERCC1 Gene Expression in Non-small Cell Lung Cancer David R. Gandara, MD,

PD-L1 Expression by Two Complementary Diagnostic Assays and mRNA In Situ Hybridization in Small Cell Lung Cancer Hui Yu, MD, PhD, Cory Batenchuk, PhD,

Assessment of EGFR Mutation Status in Lung Adenocarcinoma by Immunohistochemistry Using Antibodies Specific to the Two Major Forms of Mutant EGFR Marie.

Evaluation of Kras Gene Mutation and Copy Number in Thymic Carcinomas and Thymomas Hidefumi Sasaki, MD, PhD, Motoki Yano, MD, PhD, Yoshitaka Fujii, MD,

Tetsuya Mitsudomi, MD, Hirohito Tada, MD Journal of Thoracic Oncology

Geoffrey R. Oxnard, MD, Vincent A. Miller, MD, Mark E

MET and EGFR Mutations Identified in ALK-Rearranged Pulmonary Adenocarcinoma: Molecular Analysis of 25 ALK-Positive Cases Jennifer M. Boland, MD, Jin.

Coexistence of the BRAF Mutation and EGFR Exon 20 Insertion in a Patient with Lung Adenocarcinoma Lih-Chyun Chang, MD, Kuan-Yu Chen, MD, PhD, Jin-Yuan.

Circulating Tumor DNA Identifies EGFR Coamplification as a Mechanism of Resistance to Crizotinib in a Patient with Advanced MET-Amplified Lung Adenocarcinoma

Association of the Expression of Mutant Epidermal Growth Factor Receptor Protein as Determined with Mutation-Specific Antibodies in Non-small Cell Lung.

Innate Genetic Evolution of Lung Cancers and Spatial Heterogeneity: Analysis of Treatment-Naïve Lesions Kenichi Suda, MD, PhD, Jihye Kim, PhD, Isao Murakami,

Clinicopathologic Characteristics of the EGFR Gene Mutation in Non–small Cell Lung Cancer Anne S. Tsao, MD, Xi Ming Tang, MD, PhD, Bradley Sabloff, MD,

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

Kelsie L. Thu, BSc, Raj Chari, PhD, William W

PD-L1 Is Upregulated by Simultaneous Amplification of the PD-L1 and JAK2 Genes in Non–Small Cell Lung Cancer Seiichi Ikeda, MSc, Tatsuro Okamoto, MD,

A Sensitive ALK Immunohistochemistry Companion Diagnostic Test Identifies Patients Eligible for Treatment with Crizotinib Trish Thorne-Nuzzo, BS, Crystal.

A Phase 1/2 Trial of Ruxolitinib and Erlotinib in Patients with EGFR-Mutant Lung Adenocarcinomas with Acquired Resistance to Erlotinib Helena A. Yu,

Effusion Immunocytochemistry as an Alternative Approach for the Selection of First-Line Targeted Therapy in Advanced Lung Adenocarcinoma Tzu-Hsiu Tsai,

A Novel EML4-ALK Variant: Exon 6 of EML4 Fused to Exon 19 of ALK

Mark L. Kayton, MD, Mai He, MD, PhD, Maureen F. Zakowski, MD, Andre L

Liping Zhang, MD, Hui Yu, MD, PhD, Andrzej Badzio, MD, PhD, Theresa A

High Incidence of EGFR Mutations in Korean Men Smokers with No Intratumoral Heterogeneity of Lung Adenocarcinomas: Correlation with Histologic Subtypes,

Strategies to Improve Outcomes of Patients with EGFR-Mutant Non–Small Cell Lung Cancer: Review of the Literature Caicun Zhou, MD, PhD, Luan Di Yao, MD

LAG-3 Protein Expression in Non–Small Cell Lung Cancer and Its Relationship with PD- 1/PD-L1 and Tumor-Infiltrating Lymphocytes Yayi He, MD, PhD, Hui.

Primary Double-Strike Therapy for Cancers to Overcome EGFR Kinase Inhibitor Resistance: Proposal from the Bench Kenichi Suda, MD, PhD, Paul A. Bunn,

Do Complex Mutations of the Epidermal Growth Factor Receptor Gene Reflect Intratumoral Heterogeneity? Akito Hata, MD, Shiro Fujita, MD, PhD, Reiko Kaji,

Choroidal Metastases Responsive to Crizotinib Therapy in a Lung Adenocarcinoma Patient with ALK 2p23 Fusion Identified by ALK Immunohistochemistry Yan.

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

A Comprehensive Investigation of Molecular Features and Prognosis of Lung Adenocarcinoma with Micropapillary Component Yang Zhang, MD, Rui Wang, PhD,

A Case of ALK-Rearranged Adenocarcinoma with Small Cell Carcinoma-Like Transformation and Resistance to Crizotinib Yoon Jin Cha, MD, PhD, Byoung Chul.

Novel Epidermal Growth Factor Receptor Mutation-Specific Antibodies for Non-small Cell Lung Cancer: Immunohistochemistry as a Possible Screening Method.

ALK Translocation in Non-small Cell Lung Cancer with Adenocarcinoma and Squamous Cell Carcinoma Markers Samuel J. Klempner, MD, David W. Cohen, MD, Daniel.

Chien-Wei Chen, MD, Chin-Wei Kuo, MD Journal of Thoracic Oncology

Osimertinib for Epidermal Growth Factor Receptor Mutation–Positive Lung Adenocarcinoma That Transformed to T790M-Positive Squamous Cell Carcinoma Naoyuki.

EGFR delE709_T710insD: A Rare but Potentially EGFR Inhibitor Responsive Mutation in Non–Small-Cell Lung Cancer Allison Ackerman, MD, Michael A. Goldstein,

Validation of the IASLC/ATS/ERS Lung Adenocarcinoma Classification for Prognosis and Association with EGFR and KRAS Gene Mutations: Analysis of 440 Japanese.

Stromal Macrophage Expressing CD204 is Associated with Tumor Aggressiveness in Lung Adenocarcinoma Yoichi Ohtaki, MD, Genichiro Ishii, MD, PhD, Kanji.

Frequent BRAF or EGFR Mutations in Ciliated Muconodular Papillary Tumors of the Lung Tsugumasa Kamata, MD, Kuniko Sunami, MD, Akihiko Yoshida, MD, PhD,

Histological Subtypes of Lung Adenocarcinoma Have Differential 18F- Fluorodeoxyglucose Uptakes on the Positron Emission Tomography/Computed Tomography.

Ly6/uPAR-Related Protein C4

PTEN and PIK3CA Expression Is Associated with Prolonged Survival after Gefitinib Treatment in EGFR-Mutated Lung Cancer Patients Hideki Endoh, MD, PhD,

Driven by Mutations: The Predictive Value of Mutation Subtype in EGFR-Mutated Non– Small Cell Lung Cancer Emily Castellanos, MD, Emily Feld, MD, Leora.

Concomitant Epidermal Growth Factor Receptor Mutation and EML4-ALK Fusion in a Patient with Multifocal Lung Adenocarcinomas Jun Fan, MD Journal of Thoracic.

Unusual Chemosensitivity of Advanced Bronchioalveolar Carcinoma after Gefitinib Response and Progression: A Case Report Rafal Dziadziuszko, MD, PhD,

Activation of MET by Gene Amplification or by Splice Mutations Deleting the Juxtamembrane Domain in Primary Resected Lung Cancers Ryoichi Onozato, MD,

EGFR Mutations in Squamous Cell Lung Cancer in Never-Smokers

Thymidylate Synthase Protein Expression by IHC and Gene Copy Number by SISH Correlate and Show Great Variability in Non–Small Cell Lung Cancer Murry.

The Clinical Impact of Solid and Micropapillary Patterns in Resected Lung Adenocarcinoma Naoki Yanagawa, MD, PhD, Satoshi Shiono, MD, PhD, Masami Abiko,

Tissue Heterogeneity of EGFR Mutation in Lung Adenocarcinoma

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,

Circulating Tumor DNA Identifies EGFR Coamplification as a Mechanism of Resistance to Crizotinib in a Patient with Advanced MET-Amplified Lung Adenocarcinoma

Presentation transcript:

Heterogeneity of EGFR Aberrations and Correlation with Histological Structures: Analyses of Therapy-Naive Isogenic Lung Cancer Lesions with EGFR Mutation Kenichi Suda, MD, PhD, Isao Murakami, MD, PhD, Hui Yu, MD, PhD, Kim Ellison, MS, Masaki Shimoji, MD, Carlo Genova, MD, Christopher J. Rivard, PhD, Tetsuya Mitsudomi, MD, PhD, Fred R. Hirsch, MD, PhD Journal of Thoracic Oncology Volume 11, Issue 10, Pages 1711-1717 (October 2016) DOI: 10.1016/j.jtho.2016.05.017 Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Lesions available in this study and representative images of immunohistochemical (IHC) staining for expression of mutant EGFR protein. (A) Schema of the available lesions. Lesions depicted in blue indicate papillary or acinar predominant adenocarcinoma; lesions depicted in purple and red indicate solid and micropapillary predominant adenocarcinomas, respectively. Despite the predominant histological subtype, all lesions except for M11 harbored micropapillary and nonmicropapillary components. (B) IHC staining for mutant EGFR that specifically recognizes the deletion E746_A750 mutation in exon 19 in lung cancer cell lines with the EGFR exon 19 deletion mutation (HCC4006 [left], PC9 [middle], and H1650 cells [right]). (C) Representative images of IHC staining for mutant EGFR in tumor specimens: 1+ staining and weak staining below the 1+ threshold staining (arrow heads) in the papillary component of M5 (left); 1+ staining in the papillary component of M10 (middle); and 2+ staining in the micropapillary component of M10 (right) are shown. Journal of Thoracic Oncology 2016 11, 1711-1717DOI: (10.1016/j.jtho.2016.05.017) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 Heterogeneity in expression of mutant-specific EGFR protein and EGFR gene copy number. (A) Expression of mutant EGFR protein was significantly higher in micropapillary components (Mann-Whitney U test, p = 0.014). M11 was excluded on account of the small number of tumor cells without clear histological evaluation. (B) EGFR gene copy number status was identical between histological components. (C) The proportions of cells with four or more EGFR gene copies are compared between micropapillary and nonmicropapillary components within each lesion. Strong correlation between these parameters is identified (R2 = 0.6863). M2 and M11 were excluded on account of inability to distinguish histological structure in silver in situ hybridization specimens. Journal of Thoracic Oncology 2016 11, 1711-1717DOI: (10.1016/j.jtho.2016.05.017) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions