{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:25:19Z","timestamp":1790832319163,"version":"4.1.0"},"reference-count":52,"publisher":"BMJ","issue":"8","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2018,4,16]]},"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:p>Smad4 or DPC4 belongs to a family of signal transduction proteins that are phosphorylated and activated by transmembrane serine-threonine receptor kinases in response to transforming growth factor beta (TGF-\u03b2) signaling via several pathways. The gene acts as a tumour suppressor gene and inactivation of <jats:italic>smad4\/DPC4<\/jats:italic> is best recognised in pancreatic cancer. However, <jats:italic>smad4\/DPC4<\/jats:italic> is also mutated in other conditions and cancers such as juvenile polyposis syndrome with and without hereditary haemorrhagic telangiectasia, colorectal and prostate cancers.<\/jats:p>\n               <jats:p>Immunohistochemistry for smad4\/DPC4 protein is most useful in separating benign\/reactive conditions from pancreatic cancer in needle\/core biopsies. In normal and reactive states, the protein is localised to the cytoplasm and nucleus, while the protein is lost in high-grade pancreatic intraepithelial neoplasia\/carcinoma in situ and pancreatic cancer.<\/jats:p>","DOI":"10.1136\/jclinpath-2018-205095","type":"journal-article","created":{"date-parts":[[2018,5,2]],"date-time":"2018-05-02T12:32:50Z","timestamp":1525264370000},"page":"661-664","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":69,"title":["Smad4\/DPC4"],"prefix":"10.1136","volume":"71","author":[{"given":"Aoife J","family":"McCarthy","sequence":"first","affiliation":[{"name":"Laboratory Medicine Program, Department of Anatomical Pathology, University Health Network and University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2124-515X","authenticated-orcid":false,"given":"Runjan","family":"Chetty","sequence":"additional","affiliation":[{"name":"Laboratory Medicine Program, Department of Anatomical Pathology, University Health Network and University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2018,5,2]]},"reference":[{"key":"2025092501320614000_71.8.661.1","doi-asserted-by":"crossref","DOI":"10.1016\/S0092-8674(00)81335-5","article-title":"Nomenclature: vertebrate mediators of TGFbeta family signals","volume":"87","author":"Derynck","year":"1996","journal-title":"Cell"},{"key":"2025092501320614000_71.8.661.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.12.028"},{"key":"2025092501320614000_71.8.661.3","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5247.350"},{"key":"2025092501320614000_71.8.661.4","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-014-2883-z"},{"key":"2025092501320614000_71.8.661.5","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)01066-0"},{"key":"2025092501320614000_71.8.661.6","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.23.3157"},{"key":"2025092501320614000_71.8.661.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.09.020"},{"key":"2025092501320614000_71.8.661.8","doi-asserted-by":"crossref","DOI":"10.1080\/23723556.2015.1025181","article-title":"Point mutations in the tumor suppressor Smad4\/DPC4 enhance its phosphorylation by GSK3 and reversibly inactivate TGF-\u03b2 signaling","volume":"3","author":"Demagny","year":"2016","journal-title":"Mol Cell Oncol"},{"key":"2025092501320614000_71.8.661.9","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1097\/DCR.0b013e31825aad32","article-title":"The prevalence of hereditary hemorrhagic telangiectasia in juvenile polyposis syndrome","volume":"55","author":"O\u2019Malley","year":"2012","journal-title":"Dis Colon Rectum"},{"key":"2025092501320614000_71.8.661.10","first-page":"11","article-title":"Hereditary hemorrhagic telangiectasia. 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