Sakai H, Eishi Y, Li X-L, Akiyama Y, Miyake S, Takizawa T, Konishi N, Tatematsu M, Koike M, Yuasa Y
Department of Molecular Oncology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, Tokyo, Japan.
Gut. 2004 Mar;53(3):323-30. doi: 10.1136/gut.2003.026609.
Although it has been reported that intestinal metaplasia implicated in gastric carcinogenesis is induced by the ParaHox gene CDX2, it is unclear which genes are responsible for the formation of pseudopyloric glands and whether they play a role in gastric carcinogenesis. Pancreatic-duodenal homeobox 1 (PDX1) is also a ParaHox gene which contributes to the genesis and development of the pancreas, duodenum, and antrum. To clarify its significance for the formation of pseudopyloric glands and gastric carcinogenesis, we investigated expression of PDX1 and mucin in gastric carcinomas and surrounding mucosa.
Gastric carcinoma tissues from 95 patients were used for immunohistochemical analyses of PDX1, and mucins MUC6 and MUC5AC.
PDX1 was found to be frequently expressed in pseudopyloric glands and intestinal metaplasia. MUC6 was more abundant than MUC5AC in pseudopyloric glands while higher levels of MUC5AC than MUC6 were evident in intestinal metaplasia. The frequency of PDX1 positive reactivity was higher in differentiated type carcinomas (39/43, 90.7%) and T1 carcinomas (42/43, 97.7%) than in undifferentiated type (33/52, 63.5%) and T2-4 (30/52, 57.7%) carcinomas. PDX1 and MUC6 double positive expression was observed in carcinomas, respectively, including the corpus, and also correlated with histological type and depth of invasion. In contrast, no link was apparent between PDX1 and MUC5AC double positive reactivity and histological type.
Our study suggests that PDX1 plays an important role in the development of pseudopyloric glands, and that pseudopyloric glands may reflect a condition associated with gastric carcinogenesis.
尽管已有报道称参与胃癌发生的肠化生是由副同源盒基因CDX2诱导产生的，但尚不清楚哪些基因负责假幽门腺的形成，以及它们是否在胃癌发生中发挥作用。胰十二指肠同源盒1（PDX1）也是一种副同源盒基因，它参与胰腺、十二指肠和胃窦的发生与发育。为阐明其对假幽门腺形成及胃癌发生的意义，我们研究了PDX1和黏蛋白在胃癌及周围黏膜中的表达情况。
采用95例患者的胃癌组织进行PDX1、黏蛋白MUC6和MUC5AC的免疫组织化学分析。
发现PDX1在假幽门腺和肠化生中频繁表达。在假幽门腺中，MUC6比MUC5AC更丰富，而在肠化生中，MUC5AC水平高于MUC6。分化型癌（39/43，90.7%）和T1期癌（42/43，97.7%）中PDX1阳性反应频率高于未分化型癌（33/52，63.5%）和T2 - 4期癌（30/52，57.7%）。在包括胃体部的癌组织中观察到PDX1和MUC6双阳性表达，且与组织学类型和浸润深度相关。相比之下，PDX1和MUC5AC双阳性反应与组织学类型之间无明显关联。
我们的研究表明，PDX1在假幽门腺的发育中起重要作用，且假幽门腺可能反映了一种与胃癌发生相关的状态。
