{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:05:41Z","timestamp":1790867141791,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,4,12]],"date-time":"2004-04-12T00:00:00Z","timestamp":1081728000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2004,8,20]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Aberrant promoter methylation is an important mechanism for gene silencing. In the present study, 50 Barrett's esophagus\u2010associated esophageal adenocarcinomas (ADC), 50 cardiac ADC and 50 gastric ADC were investigated by means of methylation\u2010specific real\u2010time PCR for hypermethylation in the tumor suppressor genes <jats:italic>APC<\/jats:italic>, <jats:italic>p16<\/jats:italic><jats:sup><jats:italic>INk4A<\/jats:italic><\/jats:sup> and <jats:italic>p14<\/jats:italic><jats:sup><jats:italic>ARF<\/jats:italic><\/jats:sup>. Additionally, expression of p16<jats:sup>INK4A<\/jats:sup> protein in the carcinomas was assessed using immunohistochemistry. Marked differences in hypermethylation were found between esophageal, cardiac and gastric ADC in the <jats:italic>APC<\/jats:italic> gene (78% <jats:italic>vs<\/jats:italic>. 32% <jats:italic>vs<\/jats:italic>. 84%) and in the <jats:italic>p16<\/jats:italic><jats:sup><jats:italic>INK4A<\/jats:italic><\/jats:sup> gene (54% <jats:italic>vs<\/jats:italic>. 36% <jats:italic>vs<\/jats:italic>. 10%). Hypermethylation of <jats:italic>p14<\/jats:italic><jats:sup><jats:italic>ARF<\/jats:italic><\/jats:sup> was absent from esophageal ADC and present infrequently in cardiac (2%) and gastric ADC (10%). Complete loss of p16<jats:sup>INK4A<\/jats:sup> protein expression was detectable in 45% of all tumors and was significantly associated with hypermethylation of the <jats:italic>p16<\/jats:italic><jats:sup><jats:italic>INK4A<\/jats:italic><\/jats:sup> gene (<jats:italic>p<\/jats:italic>&lt;0.0001, \u03c7<jats:sup>2<\/jats:sup>\u2010test). Our results suggest that hypermethylation of <jats:italic>p16<\/jats:italic><jats:sup><jats:italic>INK4A<\/jats:italic><\/jats:sup> and <jats:italic>APC<\/jats:italic> are frequent findings in esophageal, cardiac and gastric ADC. Additionally, the data point to a tumor specific methylation pattern in upper gastrointestinal ADC. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.20212","type":"journal-article","created":{"date-parts":[[2004,6,7]],"date-time":"2004-06-07T19:09:11Z","timestamp":1086635351000},"page":"224-228","source":"Crossref","is-referenced-by-count":61,"title":["Hypermethylation of tumor suppressor genes (<i>p16<\/i><sup><i>INK4A<\/i><\/sup>, <i>p14<\/i><sup><i>ARF<\/i><\/sup> and <i>APC<\/i>) in adenocarcinomas of the upper gastrointestinal 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