The mechanism of the development of gastric-and-intestinal mixed intestinal metaplasia-the analysis of homeobox genes in the isolated pyloric glands-

肠上皮化生（IM）作为人类胃的一种可能的恶性前病变已被广泛研究。然而，关于IM发展的发病机制及其与胃癌的关系仍存在许多问题。同源盒型基因对器官的发育和维持非常重要。在本研究中，我们评估了IM腺和胃癌的表型与胃和肠道特异性转录因子之间的关系。Sox2作为胃特异性转录因子的表达与MUC5AC、MUC6等胃表型表达密切相关，而Cdx1/Cdx2作为肠特异性转录因子与MUC2、绒毛蛋白等肠表型表达密切相关。Sox2的表达从胃(G)，通过胃肠道混合（GI），到肠(I)表型下降，而Cdx1/2在IM腺和胃癌中呈负相关，与组织学类型无关。Cdx2阳性组在晚期胃癌患者的生存率明显高于阴性组。人防御素-5（HD-5）是一种有用的Paneth细胞分化标志物，胃癌细胞的Paneth细胞分化不是单独发生的，而是伴随着胃癌组织的肠化。双染色显示GI-IM腺体同一细胞中MUC5AC-和MUC2/villin/ cd10免疫反应性共存。综上所述，我们的研究结果表明，胃和肠道特异性基因的表达对IM腺和胃癌细胞的表型表达都很重要。此外，Cdx2在晚期胃癌中是一个有用的预后和肠道表型标志物。IM可能是由于干细胞的异常分化仍然遵循一定的秩序。

Intestinal metaplasia(IM) has been extensively studied as a possible premalignant condition in the human stomach. However, many questions remain regarding the pathogenesis of IM development as well as its relationship to gastric cancers. Homeobox genes are very important for the development and maintenance of the organs. In this study, we evaluated the relation between the phenotypes and gastric and intestinal specific transcription factors in IM glands and gastric cancers. The expression of Sox2 as a gastric specific transcription factor was strongly associated with the gastric phenotypic expression such as MUC5AC and MUC6,while Cdx1/Cdx2 as intestinal specific transcription factors had a close relation to intestinal phenotypic expression as MUC2 and villin in both IM glands and gastric cancers. The expression of Sox2 decreased from gastric (G), through gastric-and-intestinal-mixed (GI), to the intestinal (I) phenotypes, while Cdx1/2 were inversely correlated in both IM glands and gastric cancers, independent of the histological types. Cdx2 positive groups had a significant better survival than the negative ones in the advanced gastric cancers. Human defensin-5(HD-5) was a useful Paneth cell differentiation marker, and Paneth cell differentiation of gastric cancer cells did not occur alone, but was accompanied by intestinalization of gastric cancer tissues. Double staining revealed coexistence of MUC5AC- and MUC2/villin/CD10-immunoreactivity in the same cell in GI-IM glands. In conclusions, our results suggest that the expression of gastric and intestinal specific genes is very important for the phenotypic expression of both IM glands and gastric cancer cells. In addition, Cdx2 is a useful prognostic and intestinal phenotypic marker in the advanced gastric cancers. IM may be due to abnormal stem cell differentiation still obeying a certain order.