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Clinical Significance of Trk Receptor Expression as a New Therapeutic Target in Hepatocellular Carcinoma

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Pathology & Oncology Research

Abstract

Oncogenic fusion of the tropomyosin receptor kinase (Trk) receptor family encoded by the NTRK gene has been found in several carcinomas. About ten targeted therapies have been developed and clinical trials are in progress. However, the results of studies on expression of the Trk receptor in HCC have not yet been published. Immunohistochemical staining was performed using anti-TrkA+B+C antibody (ab181560, Abcam) in 288 curatively resected primary HCC samples, and the correlation between Trk expression and NTRK copy number was assessed. Targeted next generation sequencing was performed in cases with Trk overexpression to detect NTRK fusion genes. Overexpression of Trk protein was observed in 21 (7.3%) of 288 cases. The Trk overexpression group showed a trend toward shorter recurrence-free survival (RFS) (p = 0.092) and overall survival (OS) (p = 0.079) than the low expression group, with frequent multicentric occurrence. Differences in RFS and OS were statistically significant in specific sub-populations including AJCC T1 stage HCCs, tumors less than 5 cm, patients without cirrhosis, tumors without vascular invasion, or Edmondson grades I and II. Trk expression was also an independent prognostic factor in both RFS and OS. Trk expression was not associated with copy number of each NTRK gene, and NTRK fusion was not detected in HCCs with Trk overexpression. Trk expression might play an important role in the development and progression of HCC, and emerging target therapy against the Trk protein could be applicable in patients with Trk-overexpressing HCC.

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Funding

This study was funded by the Samsung Medical Center intramural Grant (#SMO1161731) and the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (NRF-2017R1C1B5017890).The authors confirm independence from those.

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Authors and Affiliations

  1. Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea

    Sangjoon Choi, Sujin Park, Yoon Ah Cho, Cheol-Keun Park & Sang Yun Ha

  2. Anatomic Pathology Reference Lab, Seegene Medical Foundation, Seoul, Republic of Korea

    Cheol-Keun Park

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  1. Sangjoon Choi
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  2. Sujin Park
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Correspondence to Sang Yun Ha.

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All contributing authors have no financial support relevant to this article, and no conflict of interest to declare.

EHTICS Approval and CONSCENT to Participate

The Institutional Review Board of Samsung Medical Center approved this study and waived informed consent for this retrospective study.

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Choi, S., Park, S., Cho, Y.A. et al. Clinical Significance of Trk Receptor Expression as a New Therapeutic Target in Hepatocellular Carcinoma. Pathol. Oncol. Res. 26, 2587–2595 (2020). https://doi.org/10.1007/s12253-020-00871-7

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  • DOI: https://doi.org/10.1007/s12253-020-00871-7

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