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

我们先前的研究表明，一种新的粘蛋白抗原A3D4在胃癌和癌性肠化组织中表达，而在正常胃粘膜和慢性胃炎肠化组织中不表达。为了验证抗原是否用于诊断目的，我们使用了大量通过内窥镜活检获得的胃组织标本进行了免疫组织化学研究。A3D4抗原在腺瘤中表达，尤其在肠型腺瘤中表达频率较高，在腺瘤周围的肠化生中也有表达。值得注意的是，在慢性胃炎病例的肠化生中，约有20%的病例A3D4抗原呈阳性，其中只有部分腺体深部呈微弱免疫染色。这些数据提示，A3D4抗原阳性的肠化生病例可能属于胃腺瘤和癌的高危人群。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MUC2除了在肠化生中表达外，在再生上皮和胃癌中也有表达，尤其是肠型。除肠化生外，检测MUC2在胃癌背景粘膜中的表达具有重要意义。然后，我们用单抗91.9H显示了表达在MUC2粘蛋白核心蛋白上的磺基路易斯A在Barrette*S食管腺癌和食管腺癌中的表达。因此，这两种抗原可能分别用于分析胃和食道癌前病变。

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.