Zixiang Yu1, Haixing Wang1, Qi Song1, Jie Huang1, Jianfang Xu2, Jieakesu Su1, Hao Wang3, Lijie Tan3, Xin Wang1, Zhengzeng Jiang1, Weijie Chen1, Dongxian Jiang4, Yingyong Hou5,6,7. 1. Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China. 2. Department of Pathology, Xiamen Branch of Zhongshan Hospital, Fudan University, Xiamen, Fujian, 361015, People's Republic of China. 3. Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China. 4. Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China. jiangdongxian3@aliyun.com. 5. Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China. houyingyong@aliyun.com. 6. Department of Pathology, School of Basic Medical Sciences and Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China. houyingyong@aliyun.com. 7. Department of Pathology, Xiamen Branch of Zhongshan Hospital, Fudan University, Xiamen, Fujian, 361015, People's Republic of China. houyingyong@aliyun.com.
Abstract
PURPOSE: Rearrangement of the neurotrophic tyrosine kinase receptor (NTRK) 1 gene is a target of tropomyosin receptor kinase A (TRKA) inhibitors, and its targeted drug (larotrectinib) has been approved by the US Food and Drug Administration. We investigated the existence and prognostic importance of NTRK1 variation in esophageal squamous cell carcinoma (ESCC). METHODS: Fluorescence in situ hybridization of a NTRK1 rearrangement was conducted on 523 ESCC samples through tissue microarrays. Kaplan-Meier curves with log-rank tests were used to evaluate survival. RESULTS: We identified 8 (1.5%), 35(6.7%) and 109 (20.8%) cases with a NTRK1 rearrangement using 15%, 10% and 5% as cut-off values, respectively. We observed copy number (CN) variation of NTRK1 in some cases: 79 (15.1%) cases had a gain in NTRK1 CN ≥ 3, and 24 (4.6%) cases had NTRK1 CN ≥ 4. A NTRK1 rearrangement at the above-mentioned thresholds was not related to disease-free survival (DFS, P = 0.45, 0.47, 0.87) and overall survival (OS, P = 0.80, 0.74, 0.57), respectively. Gain in NTRK1 CN was associated with a poor prognosis irrespective of whether NTRK1 CN ≥ 4 (DFS, P = 0.015; OS, P = 0.035) or NTRK1 CN ≥ 3 (DFS, P = 0.039; OS, P = 0.025). CONCLUSION: A NTRK1 rearrangement occurred rarely in ESCC. The increased CN of NTRK1 might be a prognostic indicator for DFS and OS in patients with ESCC.
PURPOSE: Rearrangement of the neurotrophic tyrosine kinase receptor (NTRK) 1 gene is a target of tropomyosin receptor kinase A (TRKA) inhibitors, and its targeted drug (larotrectinib) has been approved by the US Food and Drug Administration. We investigated the existence and prognostic importance of NTRK1 variation in esophageal squamous cell carcinoma (ESCC). METHODS: Fluorescence in situ hybridization of a NTRK1 rearrangement was conducted on 523 ESCC samples through tissue microarrays. Kaplan-Meier curves with log-rank tests were used to evaluate survival. RESULTS: We identified 8 (1.5%), 35(6.7%) and 109 (20.8%) cases with a NTRK1 rearrangement using 15%, 10% and 5% as cut-off values, respectively. We observed copy number (CN) variation of NTRK1 in some cases: 79 (15.1%) cases had a gain in NTRK1 CN ≥ 3, and 24 (4.6%) cases had NTRK1 CN ≥ 4. A NTRK1 rearrangement at the above-mentioned thresholds was not related to disease-free survival (DFS, P = 0.45, 0.47, 0.87) and overall survival (OS, P = 0.80, 0.74, 0.57), respectively. Gain in NTRK1 CN was associated with a poor prognosis irrespective of whether NTRK1 CN ≥ 4 (DFS, P = 0.015; OS, P = 0.035) or NTRK1 CN ≥ 3 (DFS, P = 0.039; OS, P = 0.025). CONCLUSION: A NTRK1 rearrangement occurred rarely in ESCC. The increased CN of NTRK1 might be a prognostic indicator for DFS and OS in patients with ESCC.
Entities:
Keywords:
Esophageal squamous cell carcinoma (ESCC); Fluorescence in situ hybridization (FISH); Gene copy number variation; NTRK1; Prognosis; Rearrangement
Authors: Adam Kline; Pramod Kamalapathy; Katharine Bruce; Kevin Raskin; Joseph Schwab; Santiago Lozano-Calderón Journal: Ann Surg Oncol Date: 2021-05-12 Impact factor: 5.344