{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T16:01:19Z","timestamp":1783094479481,"version":"3.54.6"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T00:00:00Z","timestamp":1690502400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K15430"],"award-info":[{"award-number":["22K15430"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K07415"],"award-info":[{"award-number":["20K07415"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Tyrosine kinase (TK) alterations, such as anaplastic lymphoma kinase (<jats:italic>ALK<\/jats:italic>) fusion, neurotrophic tyrosine receptor kinase (<jats:italic>NTRK<\/jats:italic>) fusion, c\u2010ros oncogene 1 (<jats:italic>ROS1<\/jats:italic>) fusion and mesenchymal\u2013epithelial transition factor (<jats:italic>MET<\/jats:italic>) exon 14 skipping, have been reported in colorectal cancers (CRC). We have previously reported CRCs with <jats:italic>NTRK<\/jats:italic> fusion among our cohort. However, their clinicopathological features have not been fully elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Tissue microarray (TMA)\u2010based immunohistochemistry (IHC) was performed on 951 CRC lesions from 944 patients. IHC was evaluated as positive or negative for ALK and ROS1 and 0 to 3+ for c\u2010MET. For ALK and ROS1 IHC\u2010positive cases, RNA\u2010based imbalanced gene expression assays, Archer FusionPlex assays and reverse transcription\u2013polymerase chain reaction (RT\u2010PCR) followed by Sanger sequencing were performed. For c\u2010MET IHC 3+ cases, RT\u2010PCR followed by Sanger sequencing were performed. ALK IHC was positive in three cases (0.2%) and all showed imbalanced <jats:italic>ALK<\/jats:italic> gene expression. The following <jats:italic>ALK<\/jats:italic> fusions were confirmed: <jats:italic>EML4 (exon 21)::ALK (exon 20)<\/jats:italic>, <jats:italic>EML4 (exon 6)::ALK (exon 19)<\/jats:italic> and <jats:italic>HMBOX1 (exon 6)::ALK (exon 20)<\/jats:italic>. Two showed microsatellite instability\u2010high\/mismatch repair (MMR)\u2010deficient, and all were located in the right colon. ROS1 IHC was positive in one case; however, imbalanced expression and <jats:italic>ROS1<\/jats:italic> fusion was negative. Forty\u2010two cases (4.4%) showed c\u2010MET IHC3+. <jats:italic>MET<\/jats:italic> exon 14 skipping was confirmed in nine cases. All cases were microsatellite stable\/MMR\u2010proficient, and eight were located in the left colon and rectum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>CRCs with these TK alterations had distinct clinicopathological features. Together with our previous study, 15 cases (1.6%) harboured targetable TK alterations (three <jats:italic>NTRK<\/jats:italic> fusion, three <jats:italic>ALK<\/jats:italic> fusion, nine <jats:italic>MET<\/jats:italic> exon 14 skipping).<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.15015","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T08:05:12Z","timestamp":1690531512000},"page":"733-742","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Tyrosine kinase alterations in colorectal cancer with emphasis on the distinct clinicopathological characteristics"],"prefix":"10.1111","volume":"83","author":[{"given":"Soh","family":"Okano","sequence":"first","affiliation":[{"name":"Department of Human Pathology Graduate School of Medicine, Juntendo University  Tokyo 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