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Re-classification of pancreatobiliary tumors by mucin expression profile - An application to the operative indication -

通过粘蛋白表达谱对胰胆肿瘤进行重新分类-在手术适应症中的应用-

基本信息

批准号：
12470046
负责人：
YONEZAWA Suguru
金额：
$ 8.64万
依托单位：
Kagoshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

We examined the expression profiles of membrane mucins (MUC1 and MUC4) and secretory mucins (MUC2, MUC5AC and MUC6) hi many pancreatobiliary tumors, and compared the results with clinicopathological factors of the patients with those tumors.In pancreatic tumors, we examined mucins expression in invasive ductal carcinomas (IDCs) and intraductal papillary mucinous neoplasms (IPMNs) using immunohistochemistry and in situ hybridization. IPMNs were classified into two histological subtypes, "dark cell type (IPM N-D" and "clear cell type (IPMN-C). IDCs showed high expression of all the glycoforms of MUC1. IPMNs-D showed no or low expression of all the glycoforms of MUC1. IPMNs-C showed low expression of poorly glycosylated MUC1 (MUC1/DF3), but expression of glycosylated MUC1 (MUC1/HMFG-1). Expression of MUC2 was negative in IDC, high in IPMN-D and low in IPMN-C. MUC5AC was highly expressed in all the types. MUC6 expression was higher in IPMNs-C than in IDCs and IPMNs-D.In intrahepatic cholan … More giocarcinoma-mass forming type, MUC4 expression was a statistically significant independent risk factor. Mucin-producing bile duct tumors were classified into two distinct categories by the histopathological findings, morphometry and mucin expression profiles, and there was a significant difference of the survivals between the two patient groups with two different tumors. In the patients with extrahepatic bile duct carcinomas, MUC1/DF3 was the most useful prognosis indicator among the various glycoforms of MUC1 mucins. For the comparative studies with the pancreatobiliary tumors, we also studied expression profiles of mucins in the tumors of other organs such as colon, breast, etc.To investigate the expression mechanism of MUC2 in the tumors, we examined DNA methylation in promotor areas of MUC2 gene in pancreatic carcinoma cells with MUC2 + or - expression, using methylation specific PCR. The promotor area of MUC2 gene was unmethylated in pancreatic carcinoma calls with MUC2 + expression, whereas it was methylated in pancreatic carcinoma cells with MUC2 - expression. Expression mechanism of MUC2 in the pancreatic tumors may be regulated by DNA methylation in the promptor areas of MUC2 gene. We also could amplify DNA from a small amount of tissues obtained by microdissection. Less

我们检测了膜粘蛋白（MUC 1和MUC 4）和分泌粘蛋白（MUC 2、MUC 5AC和MUC 6）在多种胰胆管肿瘤中的表达，并与这些肿瘤患者的临床病理因素进行了比较。IPMNs分为两种组织学亚型，即“暗细胞型”（IPMN-D）和“透明细胞型”（IPMN-C）。IDC显示MUC 1的所有糖型的高表达。IPMNs-D显示MUC 1的所有糖型不表达或低表达。IPMNs-C显示低糖基化MUC 1（MUC 1/DF 3）的表达，但糖基化MUC 1（MUC 1/HMFG-1）的表达。MUC 2在IDC中表达阴性，在IPMN-D中表达阳性，在IPMN-C中表达阴性。MUC 5AC在各型中均呈高表达。MUC 6在IPMNs-C中的表达高于IDCs和IPMNs-D。 ...更多信息黏液黏蛋白4表达是胶质瘤-肿块形成型的独立危险因素。根据组织病理学、形态计量学和粘蛋白表达谱将产生粘蛋白的胆管肿瘤分为两种不同的类型，并且两种不同肿瘤的两个患者组之间的生存率存在显著差异。在肝外胆管癌患者中，MUC 1/DF 3是MUC 1各种糖型中最有用的预后指标。为了与胰胆管肿瘤进行比较研究，我们还研究了结肠、乳腺等其他器官肿瘤中粘蛋白的表达谱，为了探讨MUC 2在肿瘤中的表达机制，我们采用甲基化特异性PCR检测了MUC 2阳性或阴性表达的胰腺癌细胞中MUC 2基因启动子区DNA甲基化。MUC 2基因启动子区在MUC 2+表达的胰腺癌细胞中未甲基化，而在MUC 2-表达的胰腺癌细胞中甲基化。MUC 2在胰腺肿瘤中的表达机制可能是受MUC 2基因调控区DNA甲基化的调控。我们还可以从显微切割获得的少量组织中扩增DNA。少