{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:00:42Z","timestamp":1791086442391,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,11,8]],"date-time":"2005-11-08T00:00:00Z","timestamp":1131408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Barrett's associated oesophageal adenocarcinoma (EAC) is one of the most rapidly increasing malignancies in Western countries. Because of its poor prognosis, management of this disease through screening of Barrett's oesophagus (BE) patients and identification of those with a high risk of developing an adenocarcinoma seems a promising approach. Early molecular markers of malignant transformation might contribute to such screening approaches. Gene promoter methylation analysis was performed on normal, pre\u2010neoplastic, and neoplastic lesions from BE patients. All lesions of interest were sampled by microdissection from formalin\u2010fixed paraffin\u2010embedded tissue sections. We found that, in 27 adenocarcinomas, <jats:italic>APC, TIMP3, TERT, CDKN2A<\/jats:italic>, and <jats:italic>SFRP1<\/jats:italic> promoters were methylated in 93%, 65%, 64%, 48%, and 91%, respectively; in contrast <jats:italic>MLH1, RASSF1, RARB, CDH1<\/jats:italic>, and <jats:italic>FHIT<\/jats:italic> promoters were methylated in less than 5% of the tumours. In BE mucosa from patients who had progressed to adenocarcinoma (12 samples), <jats:italic>APC, TIMP3<\/jats:italic>, and <jats:italic>TERT<\/jats:italic> promoters were hypermethylated in 100%, 91%, and 92% of cases, whereas in BE mucosa from patients who had not progressed (16 samples) methylation was found only in 36%, 23%, and 17%, respectively. Furthermore, the epigenetic profile of BE with and without EAC differed significantly with, respectively, 81% and 26% of the PCR samples showing promoter hypermethylation for <jats:italic>APC, TIMP3<\/jats:italic>, and <jats:italic>TERT<\/jats:italic> (<jats:italic>p<\/jats:italic> &lt; 0.0001). Promoter methylation of <jats:italic>CDKN2A<\/jats:italic> was infrequently detected in BE samples, while <jats:italic>SFRP1<\/jats:italic> methylation was observed in all samples. Our results suggest that promoter methylation profiling of BE using multiple target genes including <jats:italic>APC, TIMP3<\/jats:italic>, and <jats:italic>TERT<\/jats:italic> might be used as a predictive marker for increased EAC risk. Copyright \u00a9 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.1884","type":"journal-article","created":{"date-parts":[[2005,11,16]],"date-time":"2005-11-16T13:23:38Z","timestamp":1132147418000},"page":"100-107","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":104,"title":["Methylation of <i>APC, TIMP3<\/i>, and <i>TERT<\/i>: a new predictive marker to distinguish Barrett's oesophagus patients at risk for malignant transformation"],"prefix":"10.1002","volume":"208","author":[{"given":"Genevi\u00e8ve","family":"Cl\u00e9ment","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Braunschweig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Pasquier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred 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