Aberrant differentiation of the gastric epithelium after inflammation and molecular epidemiological analysis of gastric cancers

1. 我们通过MSP分析原发性胃癌中CDX2的甲基化状态，并将其与患者的生活方式进行比较。58例男性患者中有20例（34.5%）出现CDX2甲基化，15例女性患者中有1例（6.7%）出现CDX2甲基化。CDX2甲基化与绿茶和十字花科蔬菜摄入量的减少以及饱食或暴饮暴食的习惯有关。我们还分析了p16/INK4a和hMLHI的甲基化状态，但它们的频率与生活方式因素无关。因此，饮食可能是决定基因甲基化状态和由此导致的致癌基因异常表达的重要因素。p21/WAF1是一种周期蛋白依赖性激酶抑制剂。CDX2以不依赖于p53的方式与p21启动子进行反激活和物理相互作用。过表达CDX2增加p21 rnRNA。这些数据表明p21是CDX2.3的转录靶点。我们应用免疫组织化学方法研究了pdx1在胃癌及其周围粘膜组织中的表达，pdx1参与了胃窦的形成。PDX1在假幽门腺中频繁表达。PDX 1阳性反应频率在分化型（39/43,90.7%）高于未分化型（33/52,63.5%）。我们的研究提示PDX - 1在假幽门腺的发育中起重要作用，假幽门腺可能与胃癌发生有关。我们用免疫组织化学方法研究了sry相关HMG盒蛋白SOX2的表达。SOX2在小凹上皮中表达强烈，表达量远高于癌组织。SOX2在胃型胃癌中的表达高于肠型胃癌。SOX2过表达诱导胃型特异性粘蛋白标志物MUc5Ac的rnRNA表达。这些发现提示SOX2可能在胃上皮的分化中起作用，SOX2可能参与胃癌的发生，尤其是胃型胃癌。少

1. We analyzed the methylation status of CDX2 in primary gastric carcinomas by MSP and compared it with the lifestyle of the patients. Methylation of CDX2 was found in 20 (34.5%) of the 58 male patients and 1 (6.7%) of the 15 female patients. CDX2 methylation was correlated with the decreased intake of green tea and cruciferous vegetables, and with full or overeating habits. We also analyzed the methylation status of p16/INK4a and hMLHI, but their frequencies were not associated with lifestyle factors. Thus, diet could be an important factor determining the methylation status of genes and the resultant aberrant expression of genes involved in carcinogenesis.2. p21/WAF1 is a cyclin-dependent kinase inhibitor. CDX2 transactivated and physically interacted with the promoter of p21 in a p53-independent manner. Overexpression of CDX2 increased p21 rnRNA. These data suggest that p21 is a transcriptional target of CDX2.3. We investigated expression of PDX 1, which contributes to development o … More f the gastric antrurn, in gastric carcinomas and surrounding mucosa by immuohistochemistry. PDX1 was frequently expressed in pseudopyloric glands. The frequency of PDX 1 positive reactivity was higher in differentiated type (39/43, 90.7%) than in undifferentiated type carcinomas (33/52, 63.5%). Our study suggested that PDX 1 plays important roles in development of pseudopyloric glands, and that pseudopyloric glands may be associated with gastric carcinogenesis.4. We investigated expression of SOX2, a SRY-related HMG box protein, by immuohistochemistry. SOX2 was strongly expressed in the foveolar epithelium, the expression being much higher than that in carcinomas. SOX2 expression was higher in the gastric type than the intestinal type of gastric cancers. Over-expression of SOX2 induced the rnRNA expression of MUc5Ac, a specific mucin marker for the gastric type. These findings indicate that SOX2 may play a role in differentiation of the gastric epithelium, and that SOX2 may be involved in gastric carcinogenesis, particularly in the gastric type. Less