Yonezawa S, Sato E
Second Department of Pathology, Kagoshima University School of Medicine, Japan.
Pathol Int. 1997 Dec;47(12):813-30. doi: 10.1111/j.1440-1827.1997.tb03713.x.
Mucins are high molecular weight glycoproteins having oligosaccharides attached to the apomucin protein backbone by O-glycosidic linkages. Biochemical studies on the structures and the organ specificities of several mucin core proteins (MUC1-MUC7) have been reported during the past several years. In the present study of pancreas and intrahepatic bile duct tumors, MUC1 mucin (membrane bound mucin detected by monoclonal antibody, DF3) was highly expressed in invasive ductal carcinomas of the pancreas (IDC) and invasive cholangiocarcinomas of the liver (ICC), which show invasive growth and a poor prognosis, but it was rarely expressed in intraductal papillary mucinous tumors of the pancreas (IPMT) and bile duct cystadenocarcinomas of the liver (BDCC), which show a favorable prognosis. In contrast, MUC2 mucin (intestinal type secretory mucin detected by polyclonal antibody, anti-MRP) was rarely expressed in IDC and ICC, whereas it was highly expressed in IPMT and BDCC. The results suggest that the differences in the expression of MUC1 and MUC2 mucins are a useful prognostic indicator of malignancy potential in the neoplasms of the pancreas and intrahepatic bile duct. Moreover, the expression of MUC1 and MUC2 mucins was a useful indicator of the malignancy potential of tumors derived from other organs, such as the ampulla of Vater, stomach and breast. In another study on the expression of several MUC1 mucin antigens with different patterns of glycosylation, sialylated-MUC1 mucin detected by monoclonal antibody, MY.1E12, was found to be expressed in all the invasive carcinomas (IDC and ICC) but was not frequently seen in the non-invasive type tumors (IPMT and BDCC), although the other types of MUC1 mucins did not show such contrast between the invasive and non-invasive type tumors. The results suggest that sialylation of MUC1 mucin is associated with invasive growth of neoplasms. In contrast, our study of the expression of MUC2 mRNA (transcript of intestinal type mucin) and MUC5AC mRNA (transcript of gastric type mucin) by in situ hybridization in the tumors of the pancreas and intrahepatic bile duct found that the non-invasive type tumors (IPMT and BDCC) synthesize MUC2 mRNA and MUC5AC mRNA, whereas most of the invasive carcinomas (IDC and ICC) do not. Furthermore, patients positive for MUC2 mRNA or MUC5AC mRNA expression in the tumors showed significantly better survival than the patients with no expression. The production of MUC2 or MUC5AC, an abundant extracellular intestinal or gastric type secretory mucin with high viscosity may be correlated, by a majority of the non-invasive type tumors, with the expansive growth of the tumors that display lower levels of invasion and metastasis.
粘蛋白是一种高分子量糖蛋白，其寡糖通过O-糖苷键连接到脱辅基粘蛋白蛋白主链上。在过去几年中，已经报道了对几种粘蛋白核心蛋白（MUC1-MUC7）的结构和器官特异性的生化研究。在目前对胰腺和肝内胆管肿瘤的研究中，MUC1粘蛋白（通过单克隆抗体DF3检测到的膜结合粘蛋白）在胰腺浸润性导管癌（IDC）和肝浸润性胆管癌（ICC）中高度表达，这些肿瘤显示浸润性生长且预后不良，但在胰腺导管内乳头状粘液性肿瘤（IPMT）和肝胆管囊腺癌（BDCC）中很少表达，后者预后良好。相反，MUC2粘蛋白（通过多克隆抗体抗MRP检测到的肠型分泌粘蛋白）在IDC和ICC中很少表达，而在IPMT和BDCC中高度表达。结果表明，MUC1和MUC2粘蛋白表达的差异是胰腺和肝内胆管肿瘤恶性潜能的有用预后指标。此外，MUC1和MUC2粘蛋白的表达是源自其他器官（如 Vater壶腹、胃和乳腺）的肿瘤恶性潜能的有用指标。在另一项关于几种具有不同糖基化模式的MUC1粘蛋白抗原表达的研究中，通过单克隆抗体MY.1E12检测到的唾液酸化MUC1粘蛋白在所有浸润性癌（IDC和ICC）中均有表达，但在非浸润性肿瘤（IPMT和BDCC）中不常见，尽管其他类型的MUC1粘蛋白在浸润性和非浸润性肿瘤之间没有这种差异。结果表明，MUC1粘蛋白的唾液酸化与肿瘤的浸润性生长有关。相反，我们通过原位杂交对胰腺和肝内胆管肿瘤中MUC2 mRNA（肠型粘蛋白转录本）和MUC5AC mRNA（胃型粘蛋白转录本）表达的研究发现，非浸润性肿瘤（IPMT和BDCC）合成MUC2 mRNA和MUC5AC mRNA，而大多数浸润性癌（IDC和ICC）不合成。此外，肿瘤中MUC2 mRNA或MUC5AC mRNA表达阳性的患者的生存率明显高于无表达的患者。MUC2或MUC5AC的产生，一种具有高粘度的丰富的细胞外肠型或胃型分泌粘蛋白，可能与大多数非浸润性肿瘤的膨胀性生长相关，这些肿瘤显示较低水平的侵袭和转移。
