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As TRK-inhibitors are approved for all solid cancers with detectable fusions involving the Neurotrophic tyrosine receptor kinase (<jats:italic>NTRK<\/jats:italic>)-genes, there has been an increased interest in optimizing testing regimes. In this project, we wanted to find the prevalence of <jats:italic>NTRK<\/jats:italic> 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 <jats:italic>NTRK-<\/jats:italic>fusion. Among 940 cases, 43 (4.6%) had positive TRK IHC, but in none of these could a <jats:italic>NTRK<\/jats:italic> 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 in squamous 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 <jats:italic>NTRK<\/jats:italic> 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 <jats:italic>NTRK<\/jats:italic>-fusions in LUSC and adenoid cystic carcinoma.<\/jats:p>","DOI":"10.1007\/s10238-023-01273-0","type":"journal-article","created":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T16:02:17Z","timestamp":1705680137000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Evaluation of NTRK expression and fusions in a large cohort of early-stage lung cancer"],"prefix":"10.1007","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7930-9153","authenticated-orcid":false,"given":"Anne Pernille Harlem","family":"Dyrbekk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdirashid Ali","family":"Warsame","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3133-5503","authenticated-orcid":false,"given":"P\u00e5l","family":"Suhrke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne Odnakk","family":"Ludahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0687-424X","authenticated-orcid":false,"given":"Nermin","family":"Zecic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9680-6329","authenticated-orcid":false,"given":"Joakim Oliu","family":"Moe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2025-4062","authenticated-orcid":false,"given":"Marius","family":"Lund-Iversen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5153-8391","authenticated-orcid":false,"given":"Odd Terje","family":"Brustugun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,19]]},"reference":[{"key":"1273_CR1","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1056\/NEJMoa1916623","volume":"383","author":"N Howlader","year":"2020","unstructured":"Howlader N, Forjaz G, Mooradian MJ, et al. 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