AnalysIs of molecular mechanism of gastric pre-cancerous lesions by using new mucin genes

新粘蛋白基因分析胃癌前病变的分子机制

基本信息

批准号：
09470141
负责人：
IMAI Kohzoh
金额：
$ 2.18万
依托单位：
Sapporo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470141/
关键词：
mucin genes gastric pre-cancerous lesions Intestinal metaplasia gastric cancer Barett esohagus 分子機構解析

项目摘要

Our previous study showed that a new mucin antigen A3D4 was expressed at the protein level in gastric cancer and intestinal metaplasia associated with cancer, but not in normal gastric mucosa and intestinal metaplasia with chronic gastritis. To verify if the antigen is of use for diagnostic purpose, we performed an immunohistochemical study using a large number of gastric tissue specimens obtained by endoscopic biopsy. Antigen A3D4 was expressed in adenoma, especially intestinal type with high frequency and in intestinal metaplasia in the vicinity of adenoma. Of note, about 20% of intestinal metaplasia with chronic gastritis cases demonstrated to be positive for antigen A3D4, where only part of the deep portion of glands were faintly immunostained. These data suggest that antigen A3D4-positive intestinal metaplasia cases may be grouped into a high risk group for gastric adenoma and cancer.It is known that MUC2 mucin is expressed in goblet cells of intestinal metaplasia, but not in normal gastric mucosa. We revealed that MUC2 was expressed in regenerative epithelia and gastric cancer, especially intestinal type, in addition to intestinal metaplasia. It will be important to examine the expression of MUC2 in the background mucosa of gastric cancer except for intestinal metaplasia. We then showed the expression of sulfo-Lewis A, which was shown expressed on MUC2 mucin core protein, in Barrette*s esophagus and esophageal adenocarcinoma by using a monoclonal antibody 91.9H.Thus, these two antigens, MUC2 and sulfo-Lewis A may be of use for analyzing the precancerous lesions of the stomach and esophagus, respectively.

我们前期的研究表明，一种新的粘蛋白抗原A3D4在胃癌和与癌症相关的肠化生中以蛋白水平表达，但在正常胃粘膜和慢性胃炎的肠化生中不表达。为了验证该抗原是否可用于诊断目的，我们使用内窥镜活检获得的大量胃组织标本进行了免疫组织化学研究。抗原A3D4在腺瘤中表达，尤其是肠型腺瘤及腺瘤附近的肠化生中表达频率较高。值得注意的是，约20%的慢性胃炎肠化生病例呈A3D4抗原阳性，其中只有部分腺体深部呈微弱免疫染色。这些数据提示抗原A3D4阳性肠化生病例可能属于胃腺瘤和胃癌的高危人群。已知MUC2粘蛋白在肠化生杯状细胞中表达，但在正常胃粘膜中不表达。我们发现，除肠化生外，MUC2还在再生上皮细胞和胃癌中表达，尤其是肠型癌。检查除肠化生以外的胃癌背景粘膜中MUC2的表达具有重要意义。然后，我们使用单克隆抗体 91.9H 显示了在 Barrette*s 食管和食管腺癌中 MUC2 粘蛋白核心蛋白上表达的 sulfo-Lewis A 的表达。因此，MUC2 和 sulfo-Lewis A 这两种抗原可能分别可用于分析胃和食道的癌前病变。