PMID- 29689458 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1936-5233 (Print) IS - 1936-5233 (Electronic) IS - 1936-5233 (Linking) VI - 11 IP - 3 DP - 2018 Jun TI - Cytoplasmic TrkA Expression as a Screen for Detecting NTRK1 Fusions in Colorectal Cancer. PG - 764-770 LID - S1936-5233(18)30047-0 [pii] LID - 10.1016/j.tranon.2018.03.011 [doi] AB - 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 >4) was associated with the presence of NTRK1 gene fusions (P<.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. CI - Copyright (c) 2018 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Choi, Yuri AU - Choi Y AD - Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, and Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-Gu, Busan 49241, Republic of Korea. FAU - Won, Yeo-Jin AU - Won YJ AD - Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, and Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-Gu, Busan 49241, Republic of Korea. FAU - Lee, Sojeong AU - Lee S AD - Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, and Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-Gu, Busan 49241, Republic of Korea. FAU - Kim, Ahrong AU - Kim A AD - Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, and Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-Gu, Busan 49241, Republic of Korea. FAU - Kim, Younggeum AU - Kim Y AD - Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, and Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-Gu, Busan 49241, Republic of Korea. FAU - Park, Won-Young AU - Park WY AD - Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, and Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-Gu, Busan 49241, Republic of Korea. FAU - Jo, Hong-Jae AU - Jo HJ AD - Department of Surgery, Pusan National University Hospital and Pusan National University School of Medicine, and Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-Gu, Busan 49241, Republic of Korea. FAU - Song, Geun Am AU - Song GA AD - Department of Internal Medicine, Pusan National University Hospital and Pusan National University School of Medicine, and Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-Gu, Busan 49241, Republic of Korea. FAU - Kwon, Chae Hwa AU - Kwon CH AD - Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, and Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-Gu, Busan 49241, Republic of Korea. FAU - Park, Do Youn AU - Park DY AD - Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, and Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-Gu, Busan 49241, Republic of Korea. Electronic address: pdy220@pusan.ac.kr. LA - eng PT - Journal Article DEP - 20180422 PL - United States TA - Transl Oncol JT - Translational oncology JID - 101472619 PMC - PMC6050437 EDAT- 2018/04/25 06:00 MHDA- 2018/04/25 06:01 PMCR- 2018/04/22 CRDT- 2018/04/25 06:00 PHST- 2018/02/02 00:00 [received] PHST- 2018/03/28 00:00 [revised] PHST- 2018/03/28 00:00 [accepted] PHST- 2018/04/25 06:00 [pubmed] PHST- 2018/04/25 06:01 [medline] PHST- 2018/04/25 06:00 [entrez] PHST- 2018/04/22 00:00 [pmc-release] AID - S1936-5233(18)30047-0 [pii] AID - 10.1016/j.tranon.2018.03.011 [doi] PST - ppublish SO - Transl Oncol. 2018 Jun;11(3):764-770. doi: 10.1016/j.tranon.2018.03.011. Epub 2018 Apr 22.