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Cytoplasmic TrkA Expression as a Screen for Detecting NTRK1 Fusions in Colorectal Cancer
  • 작성일2019-05-09
  • 최종수정일2019-05-09
  • 담당부서연구기획과
  • 연락처043-719-8033
  • 527
Translational Oncology, 2018, 11(3), 764─770, DOI: https://doi.org/10.1016/j.tranon.2018.03.011

Cytoplasmic TrkA Expression as a Screen for Detecting NTRK1 Fusions in Colorectal Cancer

Yuri Choi, Yeo-Jin Won; Sojeong Lee; Ahrong Kim; Younggeum Kim; Won-Young Park; Hong-Jae Jo; Geun Am Song; Chae Hwa Kwon; Do Youn Park

Abstract

    NTRK1 gene fusions, the targets of multikinase inhibitors, are promising therapeutic targets for colorectal cancer (CRC). However, screening methods for detecting NTRK1 gene fusions in CRC tissues have not been reported. In this study, we investigated the potential use of immunohistochemistry (IHC) for detecting NTRK1 gene fusions. We performed and compared IHC with fluorescence in situ hybridization (FISH) in 80 CRC patients. TrkA immunostaining was observed to be both membranous and cytoplasmic and was scored semiquantitatively using staining intensity and proportions. The tumors were observed to be NTRK1 gene fusion-positive when ≥20 out of 100 nuclei in FISH. A significant correlation between the IHC and FISH results for determination of the NTRK1 gene fusions was observed. We measured the cytoplasmic TrkA expression, which showed an area under the receiver operating characteristic (ROC) curve of 0.926 (range: 0.864-0.987, 95% CI, P = .001). By choosing 4.5 (sum of the intensity and proportion scores of cytoplasmic TrkA expression) as the cut-off value for the positive and negative NTRK1 gene fusion groups, the sensitivity and specificity for predicting lymph node metastasis were 100 and 83.8%, respectively (P = .001). Specifically, high cytoplasmic TrkA expression (sum of intensity and proportion scores N4) was associated with the presence of NTRK1 gene fusions (P b .0001, r = 0.528). Taken together, our data showed that IHC for TrkA can be used as an efficient screening method for detecting NTRK1 gene fusions in CRC.



  • 본 연구는 질병관리본부 연구개발과제(과제번호 2018-보건의료생물자원종합관리) 연구비를 지원받아 수행되었습니다.
  • This research was supported by a fund(code 2018-보건의료생물자원종합관리) by Research of Korea Centers for Disease Control and Prevention.


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