{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:11:56Z","timestamp":1790079116280,"version":"4.0.1"},"reference-count":36,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2026,11,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    MET is an actionable receptor tyrosine kinase, and MET\u2010directed antibody\u2013drug conjugates (ADCs) have recently entered clinical practice with FDA approval in non\u2010small cell lung cancer and are now being evaluated across gastrointestinal malignancies, with patient selection based on MET immunohistochemistry (IHC) 3+ membranous staining at varying percentage thresholds. However, robust real\u2010world data on MET protein expression and clinically relevant ADC\u2010aligned thresholds in upper GI adenocarcinomas remain limited. We profiled 1532 upper GI adenocarcinomas using the clinically validated VENTANA MET (SP44) IHC assay. MET was stratified by (i) 3+ membranous staining fractions (any, \u2265\u200910%, \u2265\u200950%) reflecting contemporary ADC eligibility concepts and (ii)\n                    <jats:italic>H<\/jats:italic>\n                    \u2010score (0\u2013300; high \u2265\u2009150). Overall survival analyses and multivariable Cox regression analyses were performed. High MET expression was uncommon (\n                    <jats:italic>H<\/jats:italic>\n                    \u2010score\u2009\u2265\u2009150: 2.3%; any 3+: 1.6%; \u2265\u200910% 3+: 1.3%; \u2265\u200950% 3+: 1.0%) and enriched in advanced T stage. MET IHC strongly predicted MET amplification (\n                    <jats:italic>H<\/jats:italic>\n                    \u2010score\u2009\u2265\u2009150: 63.6% amplified vs. 2.4% in negatives; any 3+: 75.0% vs. 2.6%; all\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Any MET 3+ staining was independently associated with inferior overall survival (adjusted HR 2.22, 95% CI 1.29\u20133.83). Most MET 3+ tumors lacked concurrent HER2 positivity, Claudin\u201018.2 expression, or dMMR\/MSI. In the largest real\u2010world cohort to date, MET overexpression identifies a rare, biologically aggressive subset with poor outcomes. By applying the latest MET\u2010ADC\u2013relevant IHC criteria (including the \u2265\u200910% 3+ threshold), this study provides clinically translatable prevalence estimates and supports standardized MET testing to inform prospective MET\u2010directed ADC trials in upper GI adenocarcinoma.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70634","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T05:06:02Z","timestamp":1783055162000},"page":"2606-2618","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>MET<\/scp>\n                    Expression in Upper Gastrointestinal Adenocarcinoma: Prevalence, Prognostic Impact, and Implications for Anti\u2010\n                    <scp>MET<\/scp>\n                    Antibody\u2010Drug Conjugate Therapy"],"prefix":"10.1002","volume":"159","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7510-2261","authenticated-orcid":false,"given":"Tillmann","family":"Bedau","sequence":"first","affiliation":[{"name":"Institute of Pathology, Faculty of Medicine and University Hospital Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Zander","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Faculty of Medicine and University Hospital Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Anton Schl\u00f6\u00dfer","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Cancer Surgery Faculty of Medicine and University Hospital of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hakan","family":"Alakus","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Cancer Surgery Faculty of Medicine and University Hospital of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onur","family":"Mustafov","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Cancer Surgery Faculty of Medicine and University Hospital of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"B\u00fcttner","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Faculty of Medicine and University Hospital Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Bruns","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Cancer Surgery Faculty of Medicine and University Hospital of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3537-6011","authenticated-orcid":false,"given":"Alexander","family":"Quaas","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Faculty of Medicine and University Hospital Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2004.04.021"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/1759\u20107714.14745"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.soncn.2008.10.005"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/EDBK_236827"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620\u2010023\u201008126\u20106"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15061656"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(10)61121\u2010X"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(21)00797\u20102"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(23)00620\u20107"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc779"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/1758834011422556"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.CD\u201019\u20101446"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3205"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045\u2010025\u201001704\u20103"},{"key":"e_1_2_11_16_1","unstructured":"U.S. FDA Approves EMRELIS (Telisotuzumab Vedotin\u2010tllv) for Adults With Previously Treated Advanced Non\u2010Small Cell Lung Cancer (NSCLC) With High c\u2010Met Protein Overexpression. AbbVie News Center \u201cU.S. FDA Approves EMRELIS (Telisotuzumab Vedotin\u2010tllv) for Adults With Previously Treated Advanced Non\u2010Small Cell Lung Cancer (NSCLC) With High c\u2010Met Protein Overexpression. AbbVie News Center \u201d(2026) https:\/\/news.abbvie.com\/2025\u201005\u201014\u2010U\u2010S\u2010FDA\u2010Approves\u2010EMRELIS\u2010TM\u2010telisotuzumab\u2010vedotin\u2010tllv\u2010for\u2010Adults\u2010With\u2010Previously\u2010Treated\u2010Advanced\u2010Non\u2010Small\u2010Cell\u2010Lung\u2010Cancer\u2010NSCLC\u2010With\u2010High\u2010c\u2010Met\u2010Protein\u2010Overexpression."},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.24.00720"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2024.42.16_suppl.3515"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2025.43.16_suppl.TPS3635"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.08.1505"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2025.43.4_suppl.490"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2025.43.16_suppl.TPS4202"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.sla.0000245847.40779.10"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10120\u2010021\u201001197\u20102"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010025\u201005635\u20107"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201014\u20100450"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885\u2010018\u20105242\u20104"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010025\u201012337\u20104"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.569475"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055\u20109965.EPI\u201010\u20101080"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annepidem.2016.05.002"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.28454"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2012.237"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2013.108"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.35.4928"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14382"},{"key":"e_1_2_11_37_1","unstructured":"Center for Drug Evaluation and Research \u201cFDA Grants Accelerated Approval to Telisotuzumab Vedotin\u2010Tllv for NSCLC With High c\u2010Met Protein Overexpression \u201d(2025) https:\/\/www.fda.gov\/drugs\/resources\u2010information\u2010approved\u2010drugs\/fda\u2010grants\u2010accelerated\u2010approval\u2010telisotuzumab\u2010vedotin\u2010tllv\u2010nsclc\u2010high\u2010c\u2010met\u2010protein\u2010overexpression."}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.70634","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.70634","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.70634","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:32:43Z","timestamp":1790076763000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.70634"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,2]]},"references-count":36,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,11,15]]}},"alternative-id":["10.1002\/ijc.70634"],"URL":"https:\/\/doi.org\/10.1002\/ijc.70634","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,2]]},"assertion":[{"value":"2026-03-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}