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Prognostic value and characterization of NTRK1 variation by fluorescence in situ hybridization in esophageal squamous cell carcinoma

  • Original Article – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

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.

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Data availability

All data generated or analyzed during this study are included in this published article.

Code availability

Not applicable.

Abbreviations

NTRK1 :

Neurotrophic Tyrosine Kinase Receptor 1

TRKA:

Tropomyosin receptor kinase A

CN:

Copy number

EC:

Esophageal carcinoma

ESCC:

Esophageal squamous cell carcinoma

RTK:

Receptor tyrosine kinase

TRK:

Tropomyosin receptor kinase

FISH:

Fluorescence in situ hybridization

TMA:

Tissue microarrays

DFS:

Disease-free survival

OS:

Overall survival

ALK :

Anaplastic lymphoma kinase

EGFR :

Epidermal growth factor receptor

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Funding

This work was financially supported by Shanghai Natural Science Foundation of China (No. 18ZR1406800), National Natural Science Foundation of China (No. 81702372), Xiamen Science and Technology Project of Fujian Province, China (No. 3502Z20184003), Shanghai Municipal Commission of Science and Technology (No. 19441904000), Shanghai Municipal Key Clinical Specialty (No. shslczdzk01302), and Shanghai Science and Technology Development Fund (No. 19MC1911000).

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Author notes

  1. Zixiang Yu and Haixing Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China

    Zixiang Yu, Haixing Wang, Qi Song, Jie Huang, Jieakesu Su, Xin Wang, Zhengzeng Jiang, Weijie Chen, Dongxian Jiang & Yingyong Hou

  2. Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China

    Hao Wang & Lijie Tan

  3. Department of Pathology, School of Basic Medical Sciences and Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China

    Yingyong Hou

  4. Department of Pathology, Xiamen Branch of Zhongshan Hospital, Fudan University, Xiamen, Fujian, 361015, People’s Republic of China

    Jianfang Xu & Yingyong Hou

Authors
  1. Zixiang Yu
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  2. Haixing Wang
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Contributions

Conceptualization: YH, DJ; Methodology: YH, DJ, QS; Formal analysis and investigation: ZY, HW, JH, XW; Writing—original draft preparation: ZY, HW, ZJ, WC; Writing—review and editing: YH, DJ, JX, JS, HW, LT; Funding acquisition: YH, DJ. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Dongxian Jiang or Yingyong Hou.

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The authors declare that they have no conflict of interest.

Ethics approval

Ethical approval was obtained from the Ethics Committee of Zhongshan Hospital of Fudan University (Shanghai, China). Our study was in accordance with the Declaration of Helsinki 1975 and its later amendments.

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Written informed consent was obtained from patients for use of their surgical specimens for research purposes.

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Yu, Z., Wang, H., Song, Q. et al. Prognostic value and characterization of NTRK1 variation by fluorescence in situ hybridization in esophageal squamous cell carcinoma. J Cancer Res Clin Oncol 147, 3113–3121 (2021). https://doi.org/10.1007/s00432-021-03578-7

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