G Lin1, C Li2, P S Li3, W Z Fang4, H P Xu1, Y H Gong3, Z F Zhu5, Y Hu6, W H Liang7, Q Chu8, W Z Zhong9, L Wu10, H J Wang11, Z J Wang12, Z M Li13, J Lin14, Y F Guan3, X F Xia3, X Yi3, Q Miao1, B Wu1, K Jiang1, X B Zheng1, W F Zhu15, X L Zheng1, P S Huang16, W J Xiao16, D Hu15, L F Zhang1, X R Fan1, T S K Mok17, C Huang1. 1. Department of Thoracic Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China. 2. Department of Pathology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China; Department of Pathology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China; Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, China. 3. Geneplus-Beijing, Beijing, China. 4. Department of Oncology, 900 Hospital of the Joint Logistics Team, Clinical Medical College of Fujian Medical University in 900 Hospital of the Joint Logistics Team, Fuzhou, China. 5. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Fudan University Shanghai Medical School, Shanghai, China. 6. Department of Medical Oncology, Chinese PLA General Hospital/Medical School of Chinese PLA, Beijing, China. 7. Department of Thoracic Oncology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Disease & China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou, China. 8. Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 9. Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China. 10. Department of Thoracic Medical Oncology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, China. 11. Henan Cancer Hospital/Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China. 12. State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. 13. Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China. 14. Department of Medical Oncology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China. 15. Department of Pathology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China. 16. Department of Pathology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China. 17. State Key Laboratory of Translational Oncology, Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: tony@clo.cuhk.edu.hk.
Abstract
BACKGROUND: Adenosquamous carcinoma (ASC) of the lung is a heterogeneous disease that is composed of both adenocarcinoma components (ACC) and squamous cell carcinoma components (SCCC). Their genomic profile, genetic origin, and clinical management remain controversial. PATIENTS AND METHODS: Resected ASC and metastatic tumor in regional lymph nodes (LNs) were collected. The ACC and SCCC were separated by microdissection of primary tumor. The 1021 cancer-related genes were evaluated by next-generation sequencing independently in ACC and SCCC and LNs. Shared and private alterations in the two components were investigated. In addition, genomic profiles of independent cohorts of adenocarcinomas and squamous cell carcinomas were examined for comparison. We have also carried out a retrospective study of ASCs with known EGFR mutation status from 11 hospitals in China for their clinical outcomes. RESULTS: The most frequent alterations in 28 surgically resected ASCs include EGFR (79%), TP53 (68%), MAP3K1 (14%) mutations, EGFR amplifications (32%), and MDM2 amplifications (18%). Twenty-seven patients (96%) had shared variations between ACC and SCCC, and pure SCCC metastases were not found in metastatic LNs among these patients. Only one patient with geographically separated ACC and SCCC had no shared mutations. Inter-component heterogeneity was a common genetic event of ACC and SCCC. The genomic profile of ASC was similar to that of 170 adenocarcinomas, but different from that of 62 squamous cell carcinomas. The incidence of EGFR mutations in the retrospective analysis of 517 ASCs was 51.8%. Among the 129 EGFR-positive patients who received EGFR-TKIs, the objective response rate was 56.6% and the median progression-free survival was 10.1 months (95% confidence interval: 9.0-11.2). CONCLUSIONS: The ACC and SCCC share a monoclonal origin, a majority with genetically inter-component heterogeneity. ASC may represent a subtype of adenocarcinoma with EGFR mutation being the most common genomic anomaly and sharing similar efficacy to EGFR TKI.
BACKGROUND:Adenosquamous carcinoma (ASC) of the lung is a heterogeneous disease that is composed of both adenocarcinoma components (ACC) and squamous cell carcinoma components (SCCC). Their genomic profile, genetic origin, and clinical management remain controversial. PATIENTS AND METHODS: Resected ASC and metastatic tumor in regional lymph nodes (LNs) were collected. The ACC and SCCC were separated by microdissection of primary tumor. The 1021 cancer-related genes were evaluated by next-generation sequencing independently in ACC and SCCC and LNs. Shared and private alterations in the two components were investigated. In addition, genomic profiles of independent cohorts of adenocarcinomas and squamous cell carcinomas were examined for comparison. We have also carried out a retrospective study of ASCs with known EGFR mutation status from 11 hospitals in China for their clinical outcomes. RESULTS: The most frequent alterations in 28 surgically resected ASCs include EGFR (79%), TP53 (68%), MAP3K1 (14%) mutations, EGFR amplifications (32%), and MDM2 amplifications (18%). Twenty-seven patients (96%) had shared variations between ACC and SCCC, and pure SCCC metastases were not found in metastatic LNs among these patients. Only one patient with geographically separated ACC and SCCC had no shared mutations. Inter-component heterogeneity was a common genetic event of ACC and SCCC. The genomic profile of ASC was similar to that of 170 adenocarcinomas, but different from that of 62 squamous cell carcinomas. The incidence of EGFR mutations in the retrospective analysis of 517 ASCs was 51.8%. Among the 129 EGFR-positive patients who received EGFR-TKIs, the objective response rate was 56.6% and the median progression-free survival was 10.1 months (95% confidence interval: 9.0-11.2). CONCLUSIONS: The ACC and SCCC share a monoclonal origin, a majority with genetically inter-component heterogeneity. ASC may represent a subtype of adenocarcinoma with EGFR mutation being the most common genomic anomaly and sharing similar efficacy to EGFR TKI.