Aberrant expression of MUC5AC and MUC6 gastric mucins and sialyl Tn antigen in intraepithelial neoplasms of the pancreas
Aberrant expression of MUC5AC and MUC6 gastric mucins and sialyl Tn antigen in intraepithelial neoplasms of the pancreas
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DOI：
10.1053/gast.2002.36018
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发表时间：
2002-10-01
期刊：
影响因子：
29.4
通讯作者：
Kim, YS
中科院分区：
文献类型：
--
作者：
Kim, GE;Bae, HK;Kim, YS
背景和目标：最近有人提出，胰腺浸润性腺癌起源于组织学上明确定义的前体导管病变，称为胰腺上皮内瘤变（PanIN-1A、-1B、-2和-3）。本研究检测了这些前体病变中几种粘蛋白基因（MUC 1、MUC 2、MUC 5AC和MUC 6）和粘蛋白相关肿瘤抗原（Nd 2和sialyl Tn）的表达模式和水平的变化。研究方法：我们用免疫组化和原位杂交方法检测了139例PanIN和68例胰腺浸润性导管腺癌。结果如下：在PanIN和浸润性导管腺癌的所有阶段均观察到MUC 1（一种泛上皮粘蛋白）和MUC 6（一种幽门腺粘蛋白）的过度表达以及MUC 5AC（一种胃小凹粘蛋白）的重新表达。与此相反，粘蛋白相关的碳水化合物抗原，唾液酸Tn的表达，显着增加，只有在PanIN-3和浸润性导管腺癌。此外，这些粘蛋白相关肽和碳水化合物抗原的表达减少与肿瘤的分化程度相关。结论：在最近定义的胰腺癌进展模型中，PanIN中胃小凹和幽门腺粘蛋白的表达是早期事件，而唾液酸Tn表达是晚期事件。这种改变的粘蛋白基因表达为胰腺癌发生中细胞系相关化生的作用提供了新的见解。
Background & Aims: It has recently been suggested that infiltrating adenocarcinoma of the pancreas arises from histologically well-defined precursor ductal lesions called pancreatic intraepithelial neoplasia (PanIN-1A, -1B, -2, and -3). This study examined alterations in the pattern and the level of expression of several mucin genes (MUC1, MUC2, MUC5AC, and MUC6) and mucin-associated tumor antigens (Nd2 and sialyl Tn) in these precursor lesions. Methods: We examined 139 PanINs and 68 infiltrating ductal adenocarcinomas of the pancreas by using immunohistochemistry and in situ hybridization methods. Results: Overexpression of MUC1, a pan-epithelial mucin, and MUC6, a pyloric-gland mucin, and de novo expression of MUC5AC, a gastric foveolar mucin, was observed in all stages of PanINs and invasive ductal adenocarcinoma. In contrast, the expression of mucin-associated carbohydrate antigen, sialyl Tn, was markedly increased only in PanIN-3 and invasive ductal adenocarcinoma. In addition, a decrease in the expression of these mucin-associated peptide and carbohydrate antigens was correlated with the degree of differentiation of the tumor. Conclusions: Expression of both gastric-foveolar and pyloric-gland mucin in PanINs is an early event, whereas sialyl Tn expression is a late event in the recently defined progression model of pancreatic carcinogenesis. This altered mucin gene expression provides new insight into the role of cell lineage-associated metaplasia in pancreatic carcinogenesis.