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Screening used immunohistochemistry (IHC); confirmation used next-generation sequencing and fluorescence in situ hybridization. Among 940 cases, 43 (4.6%) were TRK IHC-positive, yet no NTRK fusion was confirmed, and protein expression did not relate to relapse timing or overall survival. Results suggest NTRK fusions are rare and that pan-TRK IHC has substantial false positives in specific tumor types.",{"@graph":14,"@context":72},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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was the main objective of the study?","Question",{"text":62,"@type":63},"To determine the prevalence of NTRK fusions in early-stage lung cancer cases in Norway and to examine associations between TRK protein expression and specific histopathological types along with molecular and epidemiological characteristics.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"How were NTRK fusions screened and confirmed?",{"text":67,"@type":63},"TRK expression was screened using immunohistochemistry (IHC), and suspected NTRK fusions were confirmed using next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH).",{"name":69,"@type":60,"acceptedAnswer":70},"What did the study find among IHC-positive cases?",{"text":71,"@type":63},"Out of 940 cases, 43 (4.6%) were TRK IHC-positive, but none of these had an NTRK fusion confirmed by NGS or FISH, indicating a high false-positive rate for IHC in this 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[https://doi.org/10.1007/s10238-023-01273-0](https://doi.org/10.1007/s10238-023-01273-0)  \nEvaluation of NTRK expression and fusions in a large cohort of early‑stage lung cancer  \nAnne Pernille Harlem Dyrbekk1,2,3 · Abdirashid Ali Warsame4 · Pål Suhrke2 · Marianne Odnakk Ludahl5 · Nermin Zecic5 · Joakim Oliu Moe6 · Marius Lund‑Iversen4 · Odd Terje Brustugun1,3,7  \nReceived: 26 October 2023 / Accepted: 29 November 2023 / Published online: 19 January 2024 © The Author(s) 2024  \nAbstract  \nTropomyosin receptor kinases (TRK) are attractive targets for cancer therapy. As TRK-inhibitors are approved for all solid cancers with detectable fusions involving the Neurotrophic tyrosine receptor kinase (NTRK)-genes, there has been an increased interest in optimizing testing regimes. In this project, we wanted to find the prevalence of NTRK fusions in a cohort of various histopathological types of early-stage lung cancer in Norway and to investigate the association between TRK protein expression and specific histopathological types, including their molecular and epidemiological characteristics. We used immunohistochemistry (IHC) as a screening tool for TRK expression, and next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH) as confirmatory tests for underlying NTRK-fusion. Among 940 cases, 43 (4.6%) had positive TRK IHC, but in none of these could a NTRK fusion be confirmed by NGS or FISH. IHC-positive cases showed various staining intensities and patterns including cytoplasmatic or nuclear staining. IHC-positivity was more common insquamous cell carcinoma (LUSC) (10.3%) and adenoid cystic carcinoma (40.0%), where the majority showed heterogeneous staining intensity. In comparison, only 1.1% of the adenocarcinomas were positive. IHC-positivity was also more common in men, but this association could be explained by the dominance of LUSC in TRK IHC-positive cases. Protein expression was not associated with differences in time to relapse or overall survival. Our study indicates that NTRK fusion is rare in early-stage lung cancer. Due to the high level of false positive cases with IHC, Pan-TRK IHC is less suited as a screening tool for NTRK-fusions in LUSC and adenoid cystic carcinoma.  \nKeywords Lung cancer · NTRK · Immunohistochemistry · Fluorescence in situ hybridization · Next-generation sequencing · Molecular pathology  \n* Anne Pernille Harlem Dyrbekk[anndyr@siv.no](anndyr@siv.no)  \n1 University of Oslo, NO-0316 Oslo, Norway  \n2 Department of Pathology, Vestfold Hospital Trust, NO-3103 Tønsberg, Norway  \n3 Department of Cancer Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, NO-0310 Oslo, Norway  \n4 Department of Pathology, Oslo University Hospital, The Norwegian Radium Hospital, NO-0310 Oslo, Norway  \n5 Department of Microbiology/Division for Gene-Technology, Vestfold Hospital Trust, NO-3103 Tønsberg, Norway  \n6 Department of Internal Medicine, Vestfold Hospital Trust, NO-3103 Tønsberg, Norway  \n7 Department of Oncology, Vestre Viken Hospital Trust, NO-3004 Drammen, Norway  \nIntroduction  \nBiomarker driven targeted therapy has become increasingly important in cancer treatment. For lung cancer and especially for non-small cell lung carcinoma (NSCLC), it has represented a paradigm shift and has provided significant improvements in overall survival [1 , 2] . Lately, targeted therapy has become relevant also for early-stage lung cancer [3] . One such target is the Tropomyosin receptor kinase (TRK) . Neurotrophic tyrosine receptor kinase (NTRK) 1–3 are three genes that all code for a transmembrane receptor tyrosine kinase: TRK-A, TRK-B and TRK-C. NTRK gene fusions involving the kinase domain ofthe TRK protein can lead to constitutive activation of the kinase, thereby activating several signal transduction pathways that are important in carcinogenesis [4–7] .  \nTRK-inhibitors were the first drugs to get tumoragnostic approval by The European Medicin","cbCaifRwfGHqQ7y5","https://ap.wps.com/l/cbCaifRwfGHqQ7y5","pdf",1080909,"English","# Abstract\n## Study aim and rationale\n## Testing strategy (IHC screening and NGS/FISH confirmation)\n## Key findings and clinical implications\n# Introduction\n## TRK/NTRK biology and targeted therapy relevance\n## Testing approaches for NTRK fusions\n## Current prevalence knowledge in lung cancer","[{\"question\":\"What was the main objective of the study?\",\"answer\":\"To determine the prevalence of NTRK fusions in early-stage lung cancer cases in Norway and to examine associations between TRK protein expression and specific histopathological types along with molecular and epidemiological characteristics.\"},{\"question\":\"How were NTRK fusions screened and confirmed?\",\"answer\":\"TRK expression was screened using immunohistochemistry (IHC), and suspected NTRK fusions were confirmed using next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH).\"},{\"question\":\"What did the study find among IHC-positive cases?\",\"answer\":\"Out of 940 cases, 43 (4.6%) were TRK IHC-positive, but none of these had an NTRK fusion confirmed by NGS or FISH, indicating a high false-positive rate for IHC in this setting.\"}]","Evaluation of NTRK expression and fusions in a large cohort of early-stage lung cancer | PDF",1790046543,25]