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

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Presentation on theme: "Heterogeneity of EGFR Aberrations and Correlation with Histological Structures: Analyses of Therapy-Naive Isogenic Lung Cancer Lesions with EGFR Mutation "— Presentation transcript:

1 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 (October 2016) DOI: /j.jtho Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

2 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  , DOI: ( /j.jtho ) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

3 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 = ). M2 and M11 were excluded on account of inability to distinguish histological structure in silver in situ hybridization specimens. Journal of Thoracic Oncology  , DOI: ( /j.jtho ) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

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