{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:47:08Z","timestamp":1791586028293,"version":"4.3.4"},"reference-count":28,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>NTRK rearranged tumours are rare but can be successfully treated using anti\u2010TRK\u2010targeted therapies, making NTRK testing important for treatment choices in patients with advanced cancers. Pan\u2010Trk immunohistochemistry (IHC) has become a valuable and affordable screening tool in many laboratories. Unfortunately, the choice of antibodies and IHC protocols to investigate biomarkers is not standardised. In this study, we compared the performance of four pan\u2010Trk IHC methods, using three different clones, primarily in NTRK fusion\u2010positive tumours.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We studied the performance of four pan\u2010Trk IHC methods using three different clones: EPR17341 (Abcam and Ventana), EP1058Y (Abcam) and A7H6R (Cell Signaling) in 22 molecularly confirmed NTRK rearranged tumours. Additionally, selected NTRK fusion\u2010negative tumours were further included: NTRK mutated (<jats:italic>n<\/jats:italic>\u00a0=\u00a08) and amplified (n\u00a0=\u00a015) tumours as well as NTRK fusion\u2010negative tumours driven by other gene fusions, such as ALK, ROS1 and BCOR (<jats:italic>n<\/jats:italic>\u00a0=\u00a020), as well as salivary gland tumours (<jats:italic>n<\/jats:italic>\u00a0=\u00a016). Inter\u2010rater agreement of three pathologists was additionally calculated, including H\u2010score. With clone EPR17341 (Abcam in\u2010house and ready\u2010to\u2010use Ventana protocol), all molecularly confirmed NTRK1\u20133 rearranged tumours were positively detected by immunohistochemistry, while the other clones missed NTRK2\u20133 rearranged tumours. For the fusion\u2010negative cohort we found the best performance (least false\u2010positive cases) using the clone A7H6R (Cell Signalling).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Given the therapeutic importance, testing for NTRK rearrangements in daily practice has become necessary and, despite IHC being a fast and affordable tool, using it in routine diagnostics is complicated and requires a high level of expertise.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14884","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T04:07:18Z","timestamp":1676002038000},"page":"1003-1012","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["A systematic comparison of<scp>pan\u2010Trk<\/scp>immunohistochemistry assays among multiple cancer types"],"prefix":"10.1111","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5704-7721","authenticated-orcid":false,"given":"Martina","family":"Haberecker","sequence":"first","affiliation":[{"name":"Department of Pathology and Molecular Pathology University Hospital Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"T\u00f6pfer","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Pathology University Hospital Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Melega","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Pathology University Hospital Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Moch","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Pathology University Hospital Zurich Zurich Switzerland"},{"name":"Medical Faculty University Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9621-8511","authenticated-orcid":false,"given":"Chantal","family":"Pauli","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Pathology University Hospital Zurich Zurich Switzerland"},{"name":"Medical Faculty University Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/300539a0"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz383"},{"key":"e_1_2_10_4_1","first-page":"PO.20.00250","article-title":"NTRK fusions identified in pediatric tumors: the frequency, fusion partners, and clinical outcome","volume":"1","author":"Zhao X","year":"2021","journal-title":"JCO Precis. Oncol."},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1714448"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-16-1237"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergen.2021.10.007"},{"key":"e_1_2_10_8_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/PO.18.00183","article-title":"Analysis of NTRK alterations in pan\u2010cancer adult and pediatric malignancies: implications for NTRK\u2010targeted therapeutics","volume":"2018","author":"Okamura R","year":"2018","journal-title":"JCO Precis. 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