Department of Internal Medicine, Cheju Halla General Hospital, Jeju, Korea.
Gut Liver. 2011 Jun;5(2):149-53. doi: 10.5009/gnl.2011.5.2.149. Epub 2011 Jun 24.
BACKGROUND/AIMS: Gastric epithelial dysplasia is considered a precancerous lesion with a variable clinical course. There is disagreement, however, regarding histology-based diagnoses, which has led to confusion in choosing a therapeutic plan. New objective markers are needed to determine which lesions progress to true malignancy. We measured LINE-1 methylation levels, which have been reported to strongly correlate with the global methylation level in gastric epithelial dysplasia and intramucosal cancer.
A total of 145 tissue samples were analyzed by two histopathologists. All tissues were excised by therapeutic endoscopic mucosal resection and paired with adjacent normal tissue samples. A modified long interspersed nucleotide elements-combined bisulfite restriction analysis (COBRA-LINE-1) method was used.
Gastric epithelial dysplasia and intramucosal cancer tissues had significantly lower levels of LINE-1 methylation than adjacent normal gastric tissues. High-grade dysplasia and intramucosal cancer were distinguishable from low-grade dysplasia based on LINE-1 methylation levels. Furthermore, the distinction could be determined with high sensitivity and specificity, as shown by the receiver operating characteristic (ROC) curve (AUC, 0.82; 95% confidence interval, 0.74 to 0.88).
LINE-1 methylation levels may provide a diagnostic tool for identifying high-grade dysplasia and intramucosal cancer.
背景/目的:胃上皮异型增生被认为是一种具有可变临床病程的癌前病变。然而,基于组织学的诊断存在分歧,这导致了治疗计划选择的混乱。需要新的客观标志物来确定哪些病变进展为真正的恶性肿瘤。我们测量了 LINE-1 甲基化水平,据报道,该水平与胃上皮异型增生和黏膜内癌的全甲基化水平密切相关。
共有 145 个组织样本由两名组织病理学家进行分析。所有组织均通过治疗性内镜黏膜切除术切除,并与相邻的正常组织样本配对。采用改良的长散布核苷酸元件-联合亚硫酸氢盐限制分析(COBRA-LINE-1)方法。
胃上皮异型增生和黏膜内癌组织的 LINE-1 甲基化水平明显低于相邻的正常胃组织。高级别异型增生和黏膜内癌与低级别异型增生可基于 LINE-1 甲基化水平区分。此外,ROC 曲线(AUC,0.82;95%置信区间,0.74 至 0.88)显示,这种区分具有较高的敏感性和特异性。
LINE-1 甲基化水平可能为识别高级别异型增生和黏膜内癌提供一种诊断工具。