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

本实验室前期研究发现，一种新的粘蛋白抗原A3 D4在胃癌及癌旁肠化组织中有蛋白水平的表达，而在正常胃粘膜及慢性胃炎肠化组织中无表达。为了验证该抗原是否可用于诊断目的，我们使用通过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。A3 D4抗原在腺瘤中表达，尤其是肠型腺瘤和腺瘤旁肠上皮化生中表达频率较高。值得注意的是，约20%的慢性胃炎肠上皮化生病例显示抗原A3 D4阳性，其中只有部分腺体深部免疫染色微弱。这些数据表明，抗原A3 D4阳性的肠化病例可能被归为胃腺瘤和胃癌的高危组。MUC 2粘蛋白在肠化的杯状细胞中表达，而在正常胃粘膜中不表达。我们发现MUC 2在再生上皮和胃癌中表达，尤其是肠型胃癌，除肠上皮化生外。因此，检测MUC 2在除肠上皮化生以外的胃癌背景粘膜中的表达具有重要意义。用单克隆抗体91.9H检测了MUC 2核心蛋白上的sulfo-Lewis A在Barrette食管和食管腺癌中的表达，表明MUC 2和sulfo-Lewis A可分别用于分析胃癌和食管癌前病变。

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.