• Chunyan Wu, Chao Zhao, Yang Yang, Yayi He, Likun Hou, Xuefei Li, Guanghui Gao, Jingyun Shi, Shengxiang Ren, Haiqing Chu, Caicun Zhou, Jun Zhang, and Gerald Schmid-Bindert.
• *Department of Pathology, †Department of Lung Cancer and Immunology, ‡Department of Thoracic Surgery, §Department of Medical Oncology, ‖Department of Imaging, ¶Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R.China; #Department of Hematology & Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA; and **Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim of Heidelberg University, Mannheim, Germany.
• J Thorac Oncol. 2015 May 1; 10 (5): 778-83.

BackgroundThe aim of this study was to investigate the discordance rates of eight known driver mutations among multiple matched intrapulmonary ground-glass nodules (GGNs) in non-small-cell lung cancer (NSCLC) patients.MethodsTumors from 35 patients with multiple lesions resected, including confirmed NSCLC and at least one GGN, were analyzed for mutations in EGFR, KRAS, HER2, BRAF, and PIK3CA together with fusions in ALK, ROS1, and RET.ResultsFrom 35 patients, a total of 72 lesions (60 were GGNs) were analyzed. These included nine adenocarcinoma in situ, nine minimal invasive adenocarcinoma, and 54 invasive adenocarcinoma. Among them, 33 tumor lesions (45.8 %) were found harboring EGFR mutations: 13 tumors with exon 19 deletion, 18 with L858R on exon 21, and two with both exon 19 del and L858R mutation. There were 5 tumors (6.9 %) harboring EML4-ALK fusion, four HER2 mutations (5.6%), three KRAS mutations (4.2%), one ROS1 fusion and one BRAF mutation. When we used the matched tumors to determine the intertumor discrepancy, only six out of 30 patients harbored identical mutations. The discordance rate of driver mutations was 80% (24 of 30) in those patients harboring at least one of the detected driver mutations. The median disease-free survival was 41.2 months (95% confidence interval: 35.8-52.6 months) and the median overall survival was "still not reached" in this cohort.ConclusionsWe found a high discrepancy of driver mutations among NSCLC patients with GGNs and a favorable prognosis after multiple lesions resection, which support surgical resection in this situation as a reasonable approach.

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