Endoglin promoter hypermethylation identifies a field defect in human primary esophageal cancer. Issue 20 (24th July 2013)

• Record Type: Journal Article
• Authors: Jin, Zhe; Zhao, Zhenfu; Cheng, Yulan; Dong, Ming; Zhang, Xiaojing; Wang, Liang; Fan, Xinmin; Feng, Xianling; Mori, Yuriko; Meltzer, Stephen J.
• Is Part Of: Cancer. Volume 119:Issue 20(2013)
• Page Start: 3604
• Page End: 3609
• Publication Date: 2013-07-24
• Subjects: Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.28276
• Languages: English
• ISSNs: 0008-543X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="cncr28276-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>Endoglin (ENG) is a 180‐kilodalton transmembrane glycoprotein that functions as a component of the transforming growth factor‐β receptor complex. Recently, <italic>ENG</italic> promoter hypermethylation was reported in several human cancers.</p> </sec> <sec id="cncr28276-sec-0002" sec-type="section"> <title>METHODS</title> <p>The authors examined <italic>ENG</italic> promoter hypermethylation using real‐time, quantitative, methylation‐specific polymerase chain reaction in 260 human esophageal tissues.</p> </sec> <sec id="cncr28276-sec-0003" sec-type="section"> <title>RESULTS</title> <p> <italic>ENG</italic> hypermethylation demonstrated highly discriminative receiver operating characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) from normal esophagus (<italic>P</italic> < .01). It is interesting to note that <italic>ENG</italic> normalized methylation values were significantly higher in ESCC compared with normal tissue (<italic>P</italic> < .01) or EAC (<italic>P</italic> < .01). The <italic>ENG</italic> hypermethylation frequency was 46.2% in ESCC and 11.9% in normal esophageal tissue, but increased early and sequentially during EAC‐associated neoplastic progression to 13.3% in Barrett metaplasia (BE), 25% in dysplastic BE, and 26.9% in frank EAC. <italic>ENG</italic> hypermethylation was significantly higher in normal esophageal tissue from patients with ESCC (mean, 0.0186) than in normal tissue from patients with EAC (mean, 0.0117; <italic>P</italic> < .05). Treatment of KYSE220 ESCC cells with the demethylating agent 5‐aza‐2′‐deoxycytidine was found to reverse <italic>ENG</italic> methylation and reactivate <italic>ENG</italic> mRNA expression.</p> </sec> <sec id="cncr28276-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>Promoter hypermethylation of <italic>ENG</italic> appears to be a frequent, tissue‐specific event in human ESCC and exhibits a field defect with promising biomarker potential for the early detection of ESCC. In addition, <italic>ENG</italic> hypermethylation occurs in a subset of human EAC, and early during BE‐associated esophageal neoplastic progression. <bold><italic>Cancer</italic> 2013;119:3604–3609</bold>. © <italic>2013 American Cancer Society</italic>.</p> </sec> </abstract>