{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T08:13:35Z","timestamp":1788250415042,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"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":["Histopathology"],"abstract":"\n Introduction<\/jats:title>\n MET (c\u2010MET) is a receptor tyrosine kinase implicated in numerous cancers, including pancreatic neuroendocrine tumours (pNETs), by promoting cell proliferation, survival, invasion and angiogenesis. Recognizing its oncogenic potential, there is significant interest in MET\u2010targeted therapies for malignancies like pNETs, which often develop treatment resistance. Immunohistochemistry (IHC) has become a practical method for detecting MET overexpression in cancers. This study evaluates MET expression in pNETs by IHC and assesses its correlation with prognostic variables and survival outcomes.<\/jats:p>\n <\/jats:sec>\n \n Methods and results<\/jats:title>\n \n Tissue microarrays containing well\u2010differentiated neuroendocrine tumours from the gastrointestinal tract were analysed. The study included 125 pNET cores from 112 patients after application of inclusion criteria. MET expression was determined using the H\u2010score system. Different variables were assessed for H\u2010score distribution and cross\u2010tables. Survival analyses were conducted based on progression\u2010free survival and overall survival. Positive MET expression was found in 83.5% of cases. Higher MET H\u2010scores were seen in patients with lymphovascular invasion (LVI), distant metastases and higher tumour grade (\n P<\/jats:italic>\n \u2009<\u20090.05). When assessing different variables for higher MET H\u2010scores, a significant association emerged at the 150\u2010cut\u2010off\u2010point for LVI, perineural invasion, radiological evidence of progression and overall survival. For survival analysis, at a MET H\u2010score threshold of 200, high MET expression was significantly associated with shorter progression\u2010free survival (mean 8.7 versus 13.4\u2009years,\n P<\/jats:italic>\n \u2009<\u20090.05) and overall survival (mean 3.6 versus 7.7\u2009years,\n P<\/jats:italic>\n \u2009<\u20090.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Elevated MET expression is linked to adverse histopathological features and worse clinical outcomes in pNET. Standardizing MET IHC evaluation is critical as anti\u2010MET therapies develop, and identifying patients likely to benefit from these treatments remains essential.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/his.70273","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T07:19:11Z","timestamp":1788247151000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MET<\/scp>\n expression by immunohistochemistry as a biomarker in pancreatic neuroendocrine tumours"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4715-6542","authenticated-orcid":false,"given":"Felipe","family":"Carrasco\u2010Tenezaca","sequence":"first","affiliation":[{"name":"Department of Pathology Yale University School of Medicine and Yale Cancer Center New Haven Connecticut 06520 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Marciano","sequence":"additional","affiliation":[{"name":"Department of Medicine Yale University School of Medicine and Yale Cancer Center New Haven Connecticut 06520 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3940-4064","authenticated-orcid":false,"given":"Leanne M.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Surgery Yale University School of Medicine and Yale Cancer Center New Haven Connecticut 06520 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"Carmichael","sequence":"additional","affiliation":[{"name":"Department of Pathology Yale University School of Medicine and Yale Cancer Center New Haven Connecticut 06520 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4972-6705","authenticated-orcid":false,"given":"Guannan","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Medicine Yale University School of Medicine and Yale Cancer Center New Haven Connecticut 06520 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2618-4173","authenticated-orcid":false,"given":"John","family":"Kunstman","sequence":"additional","affiliation":[{"name":"Department of Surgery Yale University School of Medicine and Yale Cancer Center New Haven Connecticut 06520 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8814-1702","authenticated-orcid":false,"given":"David","family":"Klimstra","sequence":"additional","affiliation":[{"name":"Department of Pathology Yale University School of Medicine and Yale Cancer Center New Haven Connecticut 06520 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1613-3919","authenticated-orcid":false,"given":"Pamela L.","family":"Kunz","sequence":"additional","affiliation":[{"name":"Department of Medicine Yale University School of Medicine and Yale Cancer Center New Haven Connecticut 06520 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3823-5337","authenticated-orcid":false,"given":"Po\u2010Han","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology Yale University School of Medicine and Yale Cancer Center New Haven Connecticut 06520 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1744-8568","authenticated-orcid":false,"given":"Samuel G.","family":"Katz","sequence":"additional","affiliation":[{"name":"Department of Pathology Yale University School of Medicine and Yale Cancer Center New Haven Connecticut 06520 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0170798","article-title":"MET\u2010EGFR dimerization in lung adenocarcinoma is dependent on EGFR mtations and altered by MET kinase inhibition","volume":"12","author":"Ortiz\u2010Zapater E","year":"2017","journal-title":"PLoS One"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1385\/EP:11:4:315","article-title":"Localization of hepatocyte growth factor and its receptor met in endocrine cells and related tumors of the gut and pancreas: an immunohistochemical study","volume":"11","author":"La Rosa S","year":"2000","journal-title":"Endocr. Pathol."},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1101\/cshperspect.a009209","article-title":"MET: a critical player in tumorigenesis and therapeutic target","volume":"5","author":"Graveel CR","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"e_1_2_11_5_1","doi-asserted-by":"crossref","DOI":"10.3390\/cancers15071976","article-title":"The role of cMET in gastric cancer\u2014a review of the literature","volume":"15","author":"Van Herpe F","year":"2023","journal-title":"Cancers (Basel)"},{"key":"e_1_2_11_6_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41698-025-01144-9","article-title":"MET (c\u2010MET) protein overexpression is an emerging protein biomarker in non\u2010small cell lung cancer","volume":"9","author":"Tsao MS","year":"2025","journal-title":"npj Precis. Oncol."},{"key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"141","DOI":"10.5230\/jgc.2016.16.3.141","article-title":"Clinicopathological significance and diagnostic accuracy of c\u2010MET expression by immunohistochemistry in gastric cancer: a meta\u2010analysis","volume":"16","author":"Pyo JS","year":"2016","journal-title":"J Gastric Cancer."},{"key":"e_1_2_11_8_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jtho.2016.10.014","article-title":"Targeting MET in Lung cancer: will expectations finally be MET?","volume":"12","author":"Drilon A","year":"2017","journal-title":"J. Thorac. Oncol."},{"key":"e_1_2_11_9_1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1158\/2159-8290.CD-11-0240","article-title":"Suppression of tumor invasion and metastasis by concurrent inhibition of c\u2010MET and VEGF signaling in pancreatic neuroendocrine tumors","volume":"2","author":"Sennino B","year":"2012","journal-title":"Cancer Discov."},{"key":"e_1_2_11_10_1","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1056\/NEJMoa2403991","article-title":"Phase 3 trial of Cabozantinib to treat advanced neuroendocrine tumors","volume":"392","author":"Chan JA","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"e_1_2_11_11_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/cancers17233837","article-title":"New treatment options for pancreatic neuroendocrine tumors: a narrative review","volume":"17","author":"Romanowicz A","year":"2025","journal-title":"Cancers (Basel)"},{"key":"e_1_2_11_12_1","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/s43018-022-00344-7","article-title":"Potent suppression of neuroendocrine tumors and gastrointestinal cancers by CDH17CAR T\u00a0cells without toxicity to normal tissues","volume":"3","author":"Feng Z","year":"2022","journal-title":"Nat. Cancer"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2025.43.4_suppl.tps844"},{"key":"e_1_2_11_14_1","doi-asserted-by":"crossref","first-page":"3000","DOI":"10.1200\/JCO.24.00720","article-title":"Telisotuzumab Vedotin monotherapy in patients with previously treated c\u2010MET protein\u2013overexpressing advanced nonsquamous EGFR\u2010Wildtype non\u2013small cell Lung cancer in the phase II LUMINOSITY trial","volume":"42","author":"Camidge DR","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"e_1_2_11_15_1","doi-asserted-by":"crossref","first-page":"73098","DOI":"10.18632\/oncotarget.20392","article-title":"Prognostic value of c\u2010MET overexpression in pancreatic adenocarcinoma: a meta\u2010analysis","volume":"8","author":"Kim JH","year":"2017","journal-title":"Oncotarget"},{"key":"e_1_2_11_16_1","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1016\/j.jtho.2019.06.009","article-title":"MET IHC is a poor screen for MET amplification or MET exon 14 mutations in Lung adenocarcinomas: data from a tri\u2010 institutional cohort of the Lung cancer mutation consortium","volume":"14","author":"Guo R","year":"2020","journal-title":"J. Thorac. Oncol."},{"issue":"16","key":"e_1_2_11_17_1","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2024.42.16_suppl.e20600","article-title":"Exploring the significance of MET overexpression by gene expression profiling versus immunohistochemistry in an EGFR\u2010mutant lung cancer cohort","volume":"42","author":"Vaid AK","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"e_1_2_11_18_1","unstructured":"Cancer; IA for R on.WHO Classification of Tumours Editorial Board. Digestive System Tumours.2019https:\/\/tumourclassification.iarc.who.int\/chaptercontent\/31\/147."},{"key":"e_1_2_11_19_1","first-page":"1","article-title":"Protocol for the examination of specimens from patients with tumors of the endocrine pancreas","volume":"2024","author":"Jain D","year":"2025","journal-title":"CAP."},{"key":"e_1_2_11_20_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1080\/00313020123290","article-title":"Immunohistochemical expression of hormone receptors in invasive breast carcinoma: correlation of results of H\u2010score with pathological parameters","volume":"33","author":"Thike AA","year":"2001","journal-title":"Pathology"},{"key":"e_1_2_11_21_1","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1038\/modpathol.2013.108","article-title":"MET overexpression assessed by new interpretation method predicts gene amplification and poor survival in advanced gastric carcinomas","volume":"26","author":"Ha SY","year":"2013","journal-title":"Mod. Pathol."},{"key":"e_1_2_11_22_1","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.cllc.2020.09.013","article-title":"Original study a phase II study of Telisotuzumab Vedotin in patients with c e MET\u2010positive stage IV or recurrent squamous cell Lung cancer (LUNG\u2010MAP sub\u2010study S1400K, NCT03574753)","volume":"22","author":"Waqar SN","year":"2021","journal-title":"Clin. Lung Cancer"},{"key":"e_1_2_11_23_1","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1530\/EC-19-0282","article-title":"Time\u2010trend and recurrence analysis of pancreatic neuroendocrine tumors","volume":"8","author":"Kim H","year":"2019","journal-title":"Endocr. Connect."},{"key":"e_1_2_11_24_1","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1369\/0022155421995600","article-title":"Impact of Preanalytical factors on the measurement of tumor tissue biomarkers using immunohistochemistry","volume":"69","author":"Bagchi A","year":"2021","journal-title":"J. Histochem. 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Pathol."},{"key":"e_1_2_11_27_1","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1111\/his.12691","article-title":"High c\u2010MET expression in stage I\u2013II pancreatic adenocarcinoma: proposal for an immunostaining scoring method and correlation with poor prognosis","volume":"67","author":"Neuzillet C","year":"2015","journal-title":"Histopathology"},{"key":"e_1_2_11_28_1","doi-asserted-by":"crossref","first-page":"3048","DOI":"10.1158\/1078-0432.CCR-15-2061","article-title":"MET amplification and exon 14 splice site mutation define unique molecular subgroups of non\u2013small cell Lung carcinoma with poor prognosis","volume":"22","author":"Tong JH","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010024\u201002184\u20108"},{"key":"e_1_2_11_30_1","first-page":"1","article-title":"c\u2010MET\u2010specific chimeric antigen receptor T\u00a0cells demonstrate anti\u2010tumor effect in c\u2010MET positive gastric cancer","volume":"13","author":"Kang CH","year":"2021","journal-title":"Cancers (Basel)"},{"key":"e_1_2_11_31_1","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1158\/2326-6066.CIR-17-0189","article-title":"Safety and efficacy of Intratumoral injections of chimeric antigen receptor (CAR) T\u00a0cells in metastatic breast cancer","volume":"5","author":"Tchou J","year":"2017","journal-title":"Cancer Immunol. Res."},{"key":"e_1_2_11_32_1","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1158\/2767-9764.CRC-22-0486","article-title":"Phase I trial of autologous RNA\u2010electroporated cMET\u2010directed CAR T\u00a0cells administered intravenously in patients with melanoma and breast carcinoma","volume":"3","author":"Shah PD","year":"2023","journal-title":"Cancer Res Commun."}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.70273","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/his.70273","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.70273","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T07:19:16Z","timestamp":1788247156000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.70273"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":31,"alternative-id":["10.1111\/his.70273"],"URL":"https:\/\/doi.org\/10.1111\/his.70273","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,1]]},"assertion":[{"value":"2026-03-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"his.70273"}}