Clinical and the Prognostic Characteristics of Lung Adenocarcinoma Patients with ROS1 Fusion in Comparison with Other Driver Mutations in East Asian Populations

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Clinical and the Prognostic Characteristics of Lung Adenocarcinoma Patients with ROS1 Fusion in Comparison with Other Driver Mutations in East Asian Populations Yen-Fu Chen, MD, Min-Shu Hsieh, MD, Shang-Gin Wu, MD, Yih-Leong Chang, MD, Jin-Yuan Shih, MD, PhD, Yi-Nan Liu, PhD, Meng- Feng Tsai, PhD, Tzu-Hsiu Tsai, MD, Chong-Jen Yu, MD, PhD, James Chih-Hsin Yang, MD, PhD, Pan-Chyr Yang, MD, PhD Journal of Thoracic Oncology Volume 9, Issue 8, Pages 1171-1179 (August 2014) DOI: 10.1097/JTO.0000000000000232 Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 Hematoxylin and eosin stain and Immunohistochemical staining (ROS1 D4D6) of ROS1 fusion-positive lung adenocarcinoma. (A, B) Case 3, surgical specimen with CD74-ROS1 fusion had diffuse and strongly (3+) cytoplasmic granular stain (100X). (C,D) Case 4, SDC4-ROS1 fusion tumors (100X) showed strong (3+), diffuse ROS1 expression in the cytoplasma. (E,F) Case 6, ROS1 protein was expressed diffusely in the cytoplasm of CD74-ROS1 fusion cell block specimen (400X). Journal of Thoracic Oncology 2014 9, 1171-1179DOI: (10.1097/JTO.0000000000000232) Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 A, Kaplan-Meier survival curve of relapse-free survival for surgical patients with lung adenocarcinoma (n = 160) in different molecular cohorts. There was no significant survival difference among the ROS1 fusion-positive patients (dotted line), epidermal growth factor receptor (EGFR) mutation-positive patients (thick line), echinoderm microtubule-associated protein-like 4 (EML4-ALK) fusion patients (thin dashed line), KRAS (thick dashed line) mutation, and quadruple-negative patients (thin line). (B) Kaplan-Meier survival curve of overall survival for surgical patients with lung adenocarcinoma (n = 160) with different molecular cohorts. There was no significant survival difference among ROS1 fusion-positive patients (dotted line), EGFR mutation-positive patients (thick line), EML4-ALK fusion patients (thin dashed line), KRAS (thick dashed line), and quadruple negative patients (thin line). MST, median survival time (months). The p value was calculated using the log-rank test. Journal of Thoracic Oncology 2014 9, 1171-1179DOI: (10.1097/JTO.0000000000000232) Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3 Kaplan-Meier survival curve of overall survival (OS) for stage IV lung adenocarcinoma patients (n = 332) with different molecular cohorts. Epidermal growth factor receptor (EGFR) mutation patients (thick line) had longer OS than patients with the echinoderm microtubule-associated protein-like 4 (EML4-ALK) fusion (thin dashed line; p = 0.039), KRAS mutation (thick dashed line; p = 0.011), and the quadruple-negative patients (thin line; p < 0.001). The ROS1 fusion-positive patients (dotted line) had potentially worse outcome than EGFR mutation patients (green line; p = 0.139), but they did not have survival differences compared with the EML4-ALK fusion, KRAS mutation, and quadruple-negative cohorts (p = 0.656, 0.435, and 0.758, respectively). MST, median survival time (months). The p value was calculated using the log-rank test. Journal of Thoracic Oncology 2014 9, 1171-1179DOI: (10.1097/JTO.0000000000000232) Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions