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Hoffmann-La Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006447","name":"University of Zurich","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006447","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virchows Arch"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Pan-Trk immunohistochemistry has become an affordable screening tool for tumors harboring <jats:italic>NTRK1 -\u20093<\/jats:italic>-rearrangements. However, false positive staining has been addressed especially in tumors with mesenchymal origin. As a positive staining triggers reflex testing, a better understanding about pan-Trk immunohistochemistry in these tumors has become necessary. In this work, we extensively studied pan-Trk IHC in a large cohort of mesenchymal neoplasms using two antibody clones: EPR17341 (RTU Assay, Roche\/Ventana) and A7H6R (Cell Signaling Technologies). Whole slide sections of 809 individual cases, including 35 subtypes of mesenchymal neoplasms, were analyzed by two different pan-Trk antibodies. Any positivity above background in\u2009&gt;\u20091% of tumor cells was classified as positive. Positive stained cases were molecularly analyzed. The specificity of clone EPR17341 was 78% and showed 21.9% false positive staining (177\/809). Forty-five percent (80\/177) of the false positive stained cases harbored a non-<jats:italic>NTRK<\/jats:italic>-gene fusion. When comparing the two antibodies in mesenchymal neoplasms, clone A7H6R showed 80% less false positive stains compared to clone EPR17341. Additionally, three tumors harboring a <jats:italic>NTRK1<\/jats:italic>-fusion were newly identified (0.4%) and reclassified in our cohort. Our work showed a high false positive rate in mesenchymal neoplasms using clone EPR17341. Clone A7H6R demonstrated a higher specificity and therefore could be considered in clinical practice for screening mesenchymal tumors for <jats:italic>NTRK1 -\u20093<\/jats:italic>-rearrangements, eventually leading to less unnecessary reflex testing.<\/jats:p>","DOI":"10.1007\/s00428-025-04102-9","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T23:47:24Z","timestamp":1744674444000},"page":"671-680","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A practical approach to better identify NTRK 1\u20133 fusion-positive mesenchymal neoplasms by pan-Trk immunohistochemistry"],"prefix":"10.1007","volume":"487","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5704-7721","authenticated-orcid":false,"given":"Martina","family":"Haberecker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Kuerten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3848-144X","authenticated-orcid":false,"given":"Viola Katharina","family":"Vetter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Malega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7986-2839","authenticated-orcid":false,"given":"Holger","family":"Moch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9621-8511","authenticated-orcid":false,"given":"Chantal","family":"Pauli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,15]]},"reference":[{"issue":"8","key":"4102_CR1","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1056\/NEJMoa1714448","volume":"378","author":"A Drilon","year":"2018","unstructured":"Drilon A, Laetsch TW, Kummar S, DuBois SG, Lassen UN, Demetri GD, Nathenson M, Doebele RC, Farago AF, Pappo AS, Turpin B, Dowlati A, Brose MS, Mascarenhas L et al (2018) Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. 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