Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies and lack of effective treatment. Gene fusions involving Neurotrophic Tyrosine Receptor Kinase 2 (NTRK2) have been proven across numerous malignancies. Anti-TRK targeted therapies provide opportunity to treat patients with NTRK2 rearranged cancers. Herein, we aimed to determine the variation and potential prognostic impact of NTRK2 in ESCC.
In 513 ESCCs resected at Zhongshan Hospital, Fudan University, from January 2007 to November 2010, NTRK2 gene variation was analyzed by Fluorescence in situ hybridization (FISH) in tissue microarrays (TMAs). Survival was estimated by Kaplan-Meier method with the log-rank test.
513 ESCC patients included 420 males and 93 females, ranged in age from 34 to 83 years (mean 61.1 year). The median follow-up time was 36 months (range: 3 to 102 months), the 5-year disease-free survival (DFS) and overall survival (OS) rate for all patients was 32.6 % and 33.1%. The translocation rate of NTRK2 in tumor cells was observed in 11.1% (57/513) and 2.34% (12/513) of patients when the cut-off value was set as low (1% ≤ translocation rate < 15%) and high (rate ≥ 15%), respectively. Survival analysis indicated that patients with high-NTRK2 translocation had a trend poorer DFS (P = 0.063) and poorer OS (P = 0.042) compared with those without NTRK2 gene translocation. Furthermore, high-NTRK2 translocation (P = 0.010) had a lower DFS compared patients without NTRK2 translocation after 18 months. Meanwhile, high-NTRK2 translocation group (P = 0.013), and low-NTRK2 translocation group (P = 0.024) had a lower OS compared patients without NTRK2 translocation after 22 months. The gene copy number (GCN) alterations of NTRK2 were observed in 36.1% (185/513), 5.8% (30/513), 1.4% (7/513) when the cut-off value was set as ≥ 2, ≥ 3, ≥ 4, respectively. We found that NTRK2 alteration was related to DFS and OS when GCN ≥ 2, it was associated with poorer 5-year survival (DFS, P = 0.019, OS, P = 0.027).
High-NTRK2 translocation in ESCC was a poor prognostic parameter especially after 18 or 22 months. Increased GCN of NTRK2 also was a poor prognostic indicator. Low-NTRK2 translocation presented in ESCC, indicating a few ESCC patients might be NTRK-targeted candidates.
Clinical trial identification
Legal entity responsible for the study
Zhongshan Hospital, Fudan University.
National Natural Science Foundation of China (No. 81702372), Shanghai Natural Science Foundation of China (No. 18ZR1406800), Shanghai Municipal Commission of Health and Family Planning, Key-developing disciplines (No. 2015ZB0201), and Shanghai Municipal Commission of Science and Technology (No. 19441904000).
All authors have declared no conflicts of interest.