Promoter methylation of E-cadherin gene in gastric mucosa associated with Helicobacter pylori infection and in gastric cancer
Promoter methylation of E-cadherin gene in gastric mucosa associated with Helicobacter pylori infection and in gastric cancer
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DOI：
10.1136/gut.52.4.502
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发表时间：
2003-04-01
期刊：
影响因子：
24.5
通讯作者：
Kwong, YL
中科院分区：
文献类型：
--
作者：
Chan, AOO;Lam, SK;Kwong, YL
背景：e -钙粘蛋白是一种参与肿瘤侵袭/转移的粘附分子。启动子CpG甲基化对e -钙粘蛋白的沉默作用已在家族性和散发性胃癌中得到证实。幽门螺杆菌是胃癌中的一类致癌物。目的：本研究旨在探讨消化不良患者胃黏膜中E-cadherin和幽门螺杆菌甲基化与胃癌手术标本中肠化生、原发性和转移性腺癌的关系。方法：采用甲基化特异性聚合酶链反应对活检组织或手术切除标本的微解剖组织进行e -钙粘蛋白甲基化研究。免疫组化法检测E-cadherin的表达。结果：消化不良患者胃粘膜中有31%（11/35）存在e -钙粘蛋白甲基化，且与幽门螺杆菌感染相关（p=0.002），但与患者年龄或有无胃炎无关。0%（0/8）的正常粘膜、57%（12/21）的肠化生、58%（15/26）的原发癌和65%（21/32）的转移性癌中存在E-cadherin甲基化。E-cadherin甲基化状态在92%（11/12）的肠化生和原发癌中一致，在85%（17/20）的原发和转移性癌中一致。胃癌中E-cadherin甲基化与肿瘤浸润深度（p=0.02）和局部淋巴结转移（p=0.05）相关。结论：e -钙粘蛋白甲基化是胃癌发生的早期事件，由幽门螺杆菌感染引发。
Background: E-cadherin is an adhesion molecule involved in tumour invasion/metastasis. Silencing of E-cadherin by promoter CpG methylation has been shown in both familial and sporadic gastric cancers. Helicobacter pylori is a class I carcinogen in gastric cancer.Aims: This study was undertaken to investigate the association between methylation of E-cadherin and H pylori in gastric mucosa from dyspeptic patients, and in intestinal metaplasia and primary and metastatic adenocarcinoma from surgical specimens of patients with gastric cancer.Methods: E-cadherin methylation was studied using methylation specific polymerase chain reaction in microdissected tissue from biopsies or surgical resection specimens. E-cadherin expression was studied by immunohistochemistry.Results: E-cadherin methylation was present in 31% (11/35) of gastric mucosae from dyspeptic patients, and was associated with H pylori infection (p=0.002), but was independent of the age of the patient or presence or absence of gastritis. E-cadherin methylation was present in 0% (0/8) of normal, mucosa, 57% (12/21) of intestinal metaplasias, and 58% (15/26) of primary and 65% (21/32) of metastatic cancers. E-cadherin methylation status was concordant in 92% (11/12) of intestinal metaplasias and primary cancers, and in 85% (17/20) of primary and metastatic cancers from the same resected specimen. E-cadherin methylation in gastric cancer was associated with depth of tumour invasion (p=0.02) and regional nodal metastasis (p=0.05).Conclusion: E-cadherin methylation is an early event in gastric carcinogenesis, and is initiated by H pylori infection.