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Recently, claudin 18.2, a transmembrane protein normally expressed in gastric mucosa, has been recognized as a novel pan-cancer therapeutic target, and several clinical trials with claudin-18-directed drugs have shown promising results on various gastrointestinal malignancies. This is the first study focusing on claudin-18 expression in small bowel adenocarcinomas. The immunohistochemical expression of claudin-18 (clone 43-14A) was assessed in 81 small bowel adenocarcinomas of diverse aetiologies and correlated with several clinico-pathologic features and patient survival. We found that 28% of adenocarcinomas were immunoreactive for claudin-18, with cutoff values of \u22651% at any intensity, while 6% of cancers showed immunoexpression of \u226575% with 2+\/3+ score. Moreover, claudin-18 (\u22651%) was positively associated with cytokeratin 7 (CK7) and MUC5AC expression, showing CK7+\/MUC5AC+ carcinomas the highest rate of positive cases, whereas a negative correlation was found between claudin-18 and CDX2 expression. In addition, some cancer-adjacent dysplastic growths and foci of gastric-type metaplasia in Crohn\u2019s disease-associated cases showed claudin-18 immunoreactivity. Survival analysis showed a non-significant trend towards a worse cancer-specific survival for claudin-18-positive cases. A fraction of small bowel adenocarcinomas, mainly sporadic or Crohn\u2019s disease-associated, and often exhibiting a non-intestinal immunoprofile, expressed claudin-18, suggesting that claudin-18-directed targeted therapy is worth investigating in such cancers.<\/jats:p>","DOI":"10.1007\/s00428-022-03393-6","type":"journal-article","created":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T04:02:21Z","timestamp":1659585741000},"page":"853-863","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Claudin-18 expression in small bowel adenocarcinoma: a clinico-pathologic study"],"prefix":"10.1007","volume":"481","author":[{"given":"Giovanni","family":"Arpa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Fassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Guerini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Quaquarini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Grillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Angerilli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenza","family":"Guzzardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Lonardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Bergamo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Vincenzo","family":"Lenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Pedrazzoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Paulli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Di Sabatino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2976-7032","authenticated-orcid":false,"given":"Alessandro","family":"Vanoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,4]]},"reference":[{"issue":"9","key":"3393_CR1","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.6004\/jnccn.2019.7344","volume":"17","author":"KS Pedersen","year":"2019","unstructured":"Pedersen KS, Raghav K, Overman MJ (2019) Small bowel adenocarcinoma: etiology, presentation, and molecular alterations. 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Informed consent was obtained for all patients enrolled in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Matteo Fassan reports personal fees (as speaker bureau or advisor) from Roche, MSD, GSK, Astellas Pharma, Diaceutics and received research grants from Astellas Pharma, QED therapeutics and macrophage pharma, unrelated to the current work. Giovanni Arpa, Camilla Guerini, Erica Quaquarini, Federica Grillo, Valentina Angerilli, Vincenza Guzzardo, Sara Lonardi, Francesca Bergamo, Marco Vincenzo Lenti, Paolo Pedrazzoli, Marco Paulli, Antonio Di Sabatino and Alessandro Vanoli have no financial or non-financial interests to declare that are relevant to the content of this article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}