Clinicopathological and Survival Analysis of Japanese Patients with Resected Non- Small-Cell Lung Cancer Harboring NKX2-1, SETDB1, MET, HER2, SOX2, FGFR1,

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Clinicopathological and Survival Analysis of Japanese Patients with Resected Non- Small-Cell Lung Cancer Harboring NKX2-1, SETDB1, MET, HER2, SOX2, FGFR1, or PIK3CA Gene Amplification Yusuke Inoue, MD, Shun Matsuura, MD, PhD, Nobuya Kurabe, PhD, Tomoaki Kahyo, PhD, Hiroki Mori, MD, PhD, Akikazu Kawase, MD, PhD, Masato Karayama, MD, PhD, Naoki Inui, MD, PhD, Kazuhito Funai, MD, PhD, Kazuya Shinmura, MD, PhD, Takafumi Suda, MD, PhD, Haruhiko Sugimura, MD, PhD Journal of Thoracic Oncology Volume 10, Issue 11, Pages 1590-1600 (November 2015) DOI: 10.1097/JTO.0000000000000685 Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 Representative fluorescence in situ hybridization (FISH) images showing the amplifications of the NKX2-1 (A), SETDB1 (B), MET(C), HER2 (D), SOX2 (E), FGFR1 (F), and PIK3CA (G) genes (in orange). The corresponding centromere enumeration probes (CEP) are shown in green. Journal of Thoracic Oncology 2015 10, 1590-1600DOI: (10.1097/JTO.0000000000000685) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 Kaplan–Meier curves for overall survival (years) stratified according to the gene amplification status of NKX2-1, SETDB1, MET, HER2, SOX2, FGFR1, and PIK3CA in non-small-cell lung cancer (NSCLC) patients. A, A significantly poorer outcome was observed for patients with NKX2-1 amplification, compared with those without amplification (log-rank, p = 0.045). B–G, No significant differences in overall survival were observed between patients with and those without SETDB1, MET, HER2, SOX2, FGFR1, and PIK3CA gene amplifications, respectively. Journal of Thoracic Oncology 2015 10, 1590-1600DOI: (10.1097/JTO.0000000000000685) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3 Kaplan–Meier estimates for overall survival (years) stratified according to NKX2-1, SETDB1, MET, and HER2 gene amplification among patients with adenocarcinoma (AC) (A–D) and stratified according to SOX2, FGFR1, and PIK3CA gene amplification among patients with squamous cell carcinoma (SCC) (E–G). A and B, Significant survival differences were observed for patients with NKX2-1 and SETDB1 amplification, compared with those without each of the gene amplifications (log-rank, p = 0.0003 and 0.011, respectively). C and D, MET amplification and HER2 amplification had no survival impact on patients with adenocarcinoma (log-rank, p = 0.53 and 0.67, respectively). E, Patients with SOX2 amplification tended to have a better survival outcome than the patients without a SOX2 copy number gain (log-rank, p = 0.13). F and G, No differences in survival were observed between SCC patients with or without FGFR1 or PIK3CA gene amplification (log-rank, p = 0.46 and 0.86, respectively). Journal of Thoracic Oncology 2015 10, 1590-1600DOI: (10.1097/JTO.0000000000000685) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions