---
title: "RNA Sequencing and Pan-TRK Immunohistochemistry to Detect NTRK Fusions in Thyroid Carcinoma"
id: "pubmed-42674723"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42674723"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42674723/"
doi: "10.21873/anticanres.18343"
published_at: "2026-09-01T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# RNA Sequencing and Pan-TRK Immunohistochemistry to Detect NTRK Fusions in Thyroid Carcinoma
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42674723
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42674723/)
- **DOI:** [10.21873/anticanres.18343](https://doi.org/10.21873%2Fanticanres.18343)
- **Published At:** 2026-09-01T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The study evaluated detection of **NTRK** gene fusions in thyroid carcinoma using gene panel testing, pan-TRK immunohistochemistry (IHC), and **RNA sequencing** to identify cases potentially missed by panel assays. - Two cohorts were analyzed: Group A (100 advanced thyroid cancer cases tested by panel) and Group B (76 surgical papillary thyroid carcinoma cases screened by IHC). - In Group A, panel testing found mitogen-activated protein kinase (MAPK) pathway alterations in 88 of 100 cases: **BRAF** mutation (n=72), RET fusion (n=8), RAS mutation (n=7), and NTRK fusion (n=1). - For Group A, pan-TRK IHC was performed and **RNA sequencing** was added for eight cases lacking MAPK alterations; RNA sequencing did not detect pathological NTRK fusions in these eight. - In Group B, IHC screening for BRAF mutation and pan-TRK identified two NTRK fusion-positive cases: one TFG-NTRK1 detected by panel testing and one **SQSTM1-NTRK3** fusion that the panel missed. - Immunostaining intensity varied by fusion: **NTRK1** fusions showed relatively strong pan-TRK staining, **NTRK3** fusions showed weak staining, and one **ETV6-NTRK3** fusion had no pan-TRK staining. - The study concludes that gene panel testing can miss certain **NTRK** fusion patterns and that active searching—using pan-TRK IHC and RNA sequencing when MAPK alterations are absent or pan-TRK is positive—may uncover additional actionable fusions. - Keywords highlighted by the authors include **BRAF mutation**, Neurotrophic tropomyosin receptor kinase fusion, papillary thyroid carcinoma, anaplastic thyroid carcinoma, and immunohistochemistry.
## Clinical Analysis & Structured Key Points
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Utility of RNA Sequencing and Immunohistochemistry for _NTRK_ Fusion in Thyroid Carcinoma [Soji Toda](https://pubmed.ncbi.nlm.nih.gov/?term=Toda+S&cauthor_id=42674723)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#full-view-affiliation-1 "Department of Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Japan.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#full-view-affiliation-2 "Cancer Biology Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan."), [Rika Kasajima](https://pubmed.ncbi.nlm.nih.gov/?term=Kasajima+R&cauthor_id=42674723)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#full-view-affiliation-3 "Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan."), [Yoichiro Okubo](https://pubmed.ncbi.nlm.nih.gov/?term=Okubo+Y&cauthor_id=42674723)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#full-view-affiliation-4 "Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan."), [Nao Saito](https://pubmed.ncbi.nlm.nih.gov/?term=Saito+N&cauthor_id=42674723)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#full-view-affiliation-2 "Cancer Biology Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan."), [Mei Kadoya](https://pubmed.ncbi.nlm.nih.gov/?term=Kadoya+M&cauthor_id=42674723)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#full-view-affiliation-1 "Department of Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Japan."), [A I Matsui](https://pubmed.ncbi.nlm.nih.gov/?term=Matsui+AI&cauthor_id=42674723)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#full-view-affiliation-5 "Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama, Japan."), [Shinya Sato](https://pubmed.ncbi.nlm.nih.gov/?term=Sato+S&cauthor_id=42674723)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#full-view-affiliation-3 "Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#full-view-affiliation-4 "Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan.")[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#full-view-affiliation-6 "Morphological Analysis Laboratory, Kanagawa Cancer Center Research Institute, Yokohama, Japan."), [Haruhiko Yamazaki](https://pubmed.ncbi.nlm.nih.gov/?term=Yamazaki+H&cauthor_id=42674723)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#full-view-affiliation-5 "Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama, Japan."), [Nobuyasu Suganuma](https://pubmed.ncbi.nlm.nih.gov/?term=Suganuma+N&cauthor_id=42674723)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#full-view-affiliation-7 "Department of Surgery, Yokohama City University, Yokohama, Japan."), [Katsuhiko Masudo](https://pubmed.ncbi.nlm.nih.gov/?term=Masudo+K&cauthor_id=42674723)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#full-view-affiliation-1 "Department of Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Japan."), [Aya Saito](https://pubmed.ncbi.nlm.nih.gov/?term=Saito+A&cauthor_id=42674723)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#full-view-affiliation-7 "Department of Surgery, Yokohama City University, Yokohama, Japan."), [Daisuke Hoshino](https://pubmed.ncbi.nlm.nih.gov/?term=Hoshino+D&cauthor_id=42674723)[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#full-view-affiliation-8 "Cancer Biology Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan; dhoshino@gancen.asahi.yokohama.jp.") Affiliations Expand ### Affiliations * 1 Department of Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Japan. * 2 Cancer Biology Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan. * 3 Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan. * 4 Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan. * 5 Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama, Japan. * 6 Morphological Analysis Laboratory, Kanagawa Cancer Center Research Institute, Yokohama, Japan. * 7 Department of Surgery, Yokohama City University, Yokohama, Japan. * 8 Cancer Biology Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan; dhoshino@gancen.asahi.yokohama.jp. * PMID: **42674723** * DOI: [ 10.21873/anticanres.18343 ](https://doi.org/10.21873/anticanres.18343) Item in Clipboard # Utility of RNA Sequencing and Immunohistochemistry for _NTRK_ Fusion in Thyroid Carcinoma Soji Toda et al. Anticancer Res. 2026 Sep. Show details Display options Display options Format Abstract PubMed PMID Anticancer Res Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Anticancer+Res%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Anticancer+Res%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42674723/) . 2026 Sep;46(9):4923-4933. doi: 10.21873/anticanres.18343. ### Authors [Soji Toda](https://pubmed.ncbi.nlm.nih.gov/?term=Toda+S&cauthor_id=42674723)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#short-view-affiliation-1 "Department of Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Japan.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#short-view-affiliation-2 "Cancer Biology Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan."), [Rika Kasajima](https://pubmed.ncbi.nlm.nih.gov/?term=Kasajima+R&cauthor_id=42674723)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#short-view-affiliation-3 "Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan."), [Yoichiro Okubo](https://pubmed.ncbi.nlm.nih.gov/?term=Okubo+Y&cauthor_id=42674723)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#short-view-affiliation-4 "Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan."), [Nao Saito](https://pubmed.ncbi.nlm.nih.gov/?term=Saito+N&cauthor_id=42674723)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#short-view-affiliation-2 "Cancer Biology Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan."), [Mei Kadoya](https://pubmed.ncbi.nlm.nih.gov/?term=Kadoya+M&cauthor_id=42674723)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#short-view-affiliation-1 "Department of Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Japan."), [A I Matsui](https://pubmed.ncbi.nlm.nih.gov/?term=Matsui+AI&cauthor_id=42674723)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#short-view-affiliation-5 "Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama, Japan."), [Shinya Sato](https://pubmed.ncbi.nlm.nih.gov/?term=Sato+S&cauthor_id=42674723)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#short-view-affiliation-3 "Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#short-view-affiliation-4 "Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan.")[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#short-view-affiliation-6 "Morphological Analysis Laboratory, Kanagawa Cancer Center Research Institute, Yokohama, Japan."), [Haruhiko Yamazaki](https://pubmed.ncbi.nlm.nih.gov/?term=Yamazaki+H&cauthor_id=42674723)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#short-view-affiliation-5 "Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama, Japan."), [Nobuyasu Suganuma](https://pubmed.ncbi.nlm.nih.gov/?term=Suganuma+N&cauthor_id=42674723)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#short-view-affiliation-7 "Department of Surgery, Yokohama City University, Yokohama, Japan."), [Katsuhiko Masudo](https://pubmed.ncbi.nlm.nih.gov/?term=Masudo+K&cauthor_id=42674723)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#short-view-affiliation-1 "Department of Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Japan."), [Aya Saito](https://pubmed.ncbi.nlm.nih.gov/?term=Saito+A&cauthor_id=42674723)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#short-view-affiliation-7 "Department of Surgery, Yokohama City University, Yokohama, Japan."), [Daisuke Hoshino](https://pubmed.ncbi.nlm.nih.gov/?term=Hoshino+D&cauthor_id=42674723)[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42674723/#short-view-affiliation-8 "Cancer Biology Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan; dhoshino@gancen.asahi.yokohama.jp.") ### Affiliations * 1 Department of Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Japan. * 2 Cancer Biology Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan. * 3 Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan. * 4 Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan. * 5 Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama, Japan. * 6 Morphological Analysis Laboratory, Kanagawa Cancer Center Research Institute, Yokohama, Japan. * 7 Department of Surgery, Yokohama City University, Yokohama, Japan. * 8 Cancer Biology Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan; dhoshino@gancen.asahi.yokohama.jp. * PMID: **42674723** * DOI: [ 10.21873/anticanres.18343 ](https://doi.org/10.21873/anticanres.18343) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Background/aim:** Neurotrophic tropomyosin receptor kinase (_NTRK_) fusion is one of the druggable driver genes of thyroid cancer, which is confirmed in surgical specimens. However, there is a risk that certain fusion patterns may not be detected using gene panel testing. This study aimed to identify patients harboring _NTRK_ fusion who might be overlooked by panel testing. **Patients and methods:** Two patient groups were analyzed. Group A included patients with advanced thyroid cancer who underwent panel testing. Immunostaining for pan-tropomyosin receptor kinase (TRK) was performed, and RNA sequencing was added to cases without mitogen-activated protein kinase alterations. Group B, including surgical cases with papillary thyroid carcinoma, was screened by immunohistochemistry for _BRAF_ mutation and pan-TRK. RNA sequencing was performed on BRAF-negative and pan-TRK-positive cases. **Results:** Among the 100 cases with advanced thyroid cancer in group A, gene panel testing detected mitogen-activated protein kinase alterations in 88. The most common alteration was the _BRAF_ mutation (n=72), followed by _RET_ fusion (8), _RAS_ mutation (7), and _NTRK_ fusion (1). Additional RNA sequencing for eight cases did not detect pathological _NTRK_ fusions. Group B included 76 cases, in which immunostaining identified two cases with _NTRK_ fusions: _TFG-NTRK1_ fusion was detected by panel testing, whereas _SQSTM1-NTRK3_ fusion was overlooked. In immunohistochemistry, _NTRK1_ fusion showed relatively strong staining, whereas _NTRK3_ showed weak staining. Notably, one case with the _ETV6-NTRK3_ fusion had no staining. **Conclusion:** This study identified a case of thyroid carcinoma harboring _NTRK_ fusion that was overlooked by panel testing. Active searching for _NTRK_ fusions is desirable in cases without mitogen-activated protein kinase abnormalities or with pan-TRK staining. **Keywords:** BRAF mutation; Neurotrophic tropomyosin receptor kinase fusion; Papillary thyroid carcinoma; anaplastic thyroid carcinoma; immunohistochemistry. Copyright © 2026 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. 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