Abstract 2285: The capability of NTRK fusion detection by next-generation sequencing/FISH/IHC in 25976 solid tumor patients

Abstract

Abstract Purpose: Despite the low prevalence of oncogenic neurotrophin receptor kinase (NTRK) fusion among most solid tumors, the encouraging results of tropomyosin receptor kinase (Trk) inhibitors such as larotrectinib and entrectinib have prompted the screening of eligible patients. Here, we aimed to report the prevalence of NTRK fusion in the Chinese solid tumor patients and to compare NTRK fusion evaluation with targeted next-generation sequencing (NGS), fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Methods: A total of 25976 tumor samples from Chinese solid tumor patients were collected between January 2017 and June 2020. All samples were assessed with targeted NGS in a CLIA-certified laboratory. NTRK genes fusions were confirmed by FISH (ZytoLight SPEC NTRK1/2/3 Dual Color Break Apart Probe) and/or pan-TRK IHC (clone EPR17341). Results: In total, 47/25976 (0.2%) patients harbored one or more NTRK fusions. NTRK fusions were found in 15 cancer types including thyroid (1/92, 1.1%), sarcoma (3/547, 0.5%), neuroendocrine (1/183, 0.5%), GIST (1/265, 0.4%), endometrium (1/274, 0.4%), esophagus (1/293, 0.3%), colorectum (14/4548, 0.3%), head neck (1/375, 0.3%), lung (16/8950, 0.2%), ovary (1/625, 0.2%), breast (1/706, 0.1%), biliary tract (2/1530, 0.1%), liver (2/2282, 0.1%), stomach (1/1505, 0.1%), and others (1/3801, 0.03%). Among these 47 patients, 11 were further confirmed by both FISH and IHC and 3 were confirmed only by IHC. 36.4% (4/11) of the patients had completely concordant NTRK status (NGS+/FISH+/IHC+). 45.5% (5/11) of the patients had consistency between NGS and FISH (NGS+/FISH+). 71.4% (10/14) of the patients had consistency between NGS and IHC (NGS+/IHC+). Moreover, there were two novel fusions includingTEX10-NTRK2 (NGS+/FISH+/IHC+) in head and neck cancer and PTPN22-NTRK1 (NGS+/IHC+) in ovarian cancer, which is the first case of ovarian cancer with NTRK fusion. Conclusions: NGS was effectively help to screen patients with novel or reported NTRK fusion, who may benefit from NTRK inhibitor therapy. And NGS showed good consistency with IHC. Further prospective study is needed to compare the impact of the NTRK status identified by NGS and IHC on NTRK inhibitors efficacy. Citation Format: Yuan Peng, Hui Chen, Xiaochen Zhao, Zhijun Han, Yuezong Bai. The capability of NTRK fusion detection by next-generation sequencing/FISH/IHC in 25976 solid tumor patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2285.