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

我们前期研究发现，一种新的粘蛋白抗原A3D4在胃癌及癌相关肠化生组织中蛋白水平表达，而在正常胃黏膜及慢性胃炎相关肠化生组织中不表达。为了验证抗原是否用于诊断目的，我们使用内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在腺瘤中以肠型表达频率高，在腺瘤附近的肠化生中表达频率高。值得注意的是，约20%的肠皮化生伴慢性胃炎病例显示抗原A3D4阳性，其中仅部分腺体深部有微弱的免疫染色。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粘蛋白在肠化生的杯状细胞中表达，而在正常胃粘膜中不表达。我们发现，除了肠化生外，MUC2在再生上皮和胃癌中表达，尤其是肠型。研究MUC2在除肠化生外的胃癌背景粘膜中的表达具有重要意义。随后，我们利用单克隆抗体91.9H检测了MUC2粘蛋白核心蛋白上表达的sulo - lewis A在Barrette食管和食管腺癌中的表达。因此，MUC2和sulo - lewis A这两种抗原可能分别用于分析胃和食道的癌前病变。

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.