Wang Fan, Xie Xin-ji, Piao Ying-shi, Liu Bin, Wang Li-dong
Department of Gastroenterology, Capital Medical University, Beijing, China.
Zhonghua Bing Li Xue Za Zhi. 2011 Aug;40(8):537-41.
To study the promoter methylation pattern of p16 and hMLH1 genes in esophageal squamous cell carcinoma and reflux esophagitis, and to correlate the results with clinical and pathologic findings.
Twelve cases of normal esophagus, 13 cases of esophageal squamous cell carcinoma, 43 cases of reflux esophagitis with basal cell hyperplasia and 21 cases of reflux esophagitis with dysplasia, as confirmed by endoscopic and pathologic examination, were enrolled into the study. Genomic DNA was extracted. The promoter methylation status of p16 was measured by methylation-specific polymerase chain reaction. The promoter methylation status of hMLH1 was measured by sodium bisulfite-restriction enzyme digestion. Immunohistochemical study for p16 and hMLH1 proteins was also carried out.
The rates of p16 methylation in normal esophageal epithelium, basal cell hyperplasia, dysplasia and esophageal squamous cell carcinoma were 0/12, 14.0% (6/43), 38.1% (8/21) and 6/13, respectively. The p16 methylation correlated with the progress of esophageal lesions. On the other hand, the hMLH1 methylation was not observed in the normal esophageal epithelium and reflux esophagitis. One case of esophageal squamous cell carcinoma showed the presence of hMLH1 methylation. The hMLH1 promoter hypermethylation did not correlate with the clinical and pathologic features.
The p16 methylation may be one of the earliest events in the pathogenesis of esophageal squamous cell carcinoma and is also observed in reflux esophagitis. Reflux esophagitis may be related to the development of esophageal squamous cell carcinoma in Chinese population. In contrast, hMLH1 methylation may not be directly involved in the tumorigenesis of esophageal squamous cell carcinoma.
研究食管鳞状细胞癌和反流性食管炎中p16和hMLH1基因的启动子甲基化模式，并将结果与临床和病理发现相关联。
纳入经内镜和病理检查确诊的12例正常食管、13例食管鳞状细胞癌、43例伴有基底细胞增生的反流性食管炎和21例伴有发育异常的反流性食管炎患者。提取基因组DNA。采用甲基化特异性聚合酶链反应检测p16的启动子甲基化状态。采用亚硫酸氢盐限制性内切酶消化法检测hMLH1的启动子甲基化状态。同时进行p16和hMLH1蛋白的免疫组织化学研究。
正常食管上皮、基底细胞增生、发育异常和食管鳞状细胞癌中p16甲基化率分别为0/12、14.0%（6/43）、38.1%（8/21）和6/13。p16甲基化与食管病变进展相关。另一方面，在正常食管上皮和反流性食管炎中未观察到hMLH1甲基化。1例食管鳞状细胞癌显示存在hMLH1甲基化。hMLH1启动子高甲基化与临床和病理特征无关。
p16甲基化可能是食管鳞状细胞癌发病机制中最早的事件之一，在反流性食管炎中也有观察到。在中国人群中，反流性食管炎可能与食管鳞状细胞癌的发生有关。相比之下，hMLH1甲基化可能不直接参与食管鳞状细胞癌的肿瘤发生。
