Expression And Clinical Value Of Gastric Cancer-associated Antigen MG7 And COX-2 In Gastric Precancerous Lesions

The development of gastric cancer is a multi-step and multi-factor involved process. The transformation of normal gastric mucosal cells into malignant cells can not be finished at one time, and it may take many steps. Intestinal metaplasia and dysplasia in gastric mucosa are the common steps in the development of gastric cancer, which are known as gastric precancerous lesions.MG7, a monoclonal antibody against gastric cancer was firstly established in our institute, by immunizing the BALB/C mice directly with a poorly-differentiated gastric adenocarcinoma cell line MKN-46-9. The antigen recognized by the antibody is different from other gastrointestinal tumor markers as reported. It has been considered as a promising biomarker in gastric cancer screening because of its high specificity. Prelimary studies had shown that the level of MG7-Ag expression was valuable in predicting and diagnosis of gastric cancer. Cyclooxygenase (COX) is a rate-limiting enzyme controlling the conversion of arachidonic acid to prostaglandinH2. The two major types of COXs are COX-1 and COX-2. The role of COX-2 in inflammation and cancer has been studied intensively. Previous studies revealed that the expression of COX-2 was closely related to the development of gastric cancer, and our laboratory further discovered COX-2 had a positive correlation with MG7-Ag in gastric cancer. However, the relationship between expression of COX-2 and MG7-Ag in gastric precancerous lesions remained unclear.In this study, we investigated the gastric cancer-associated antigen MG7 expression in 334 gastric precancerous lesions and the correlation with expression of COX-2 by immunohistochemical analysis. In addition, a one-year follow-up of 107 patients was conducted to explore the clinical value of combined detection of MG7-Ag and COX-2 in prediction of advances in gastric precancerous lesions.Objectives:To explore the significance of detection of MG7-antigen and COX-2 in gastric precancerous lesions and the correlation between the two molecules. To explore the clinical value of combined detection of MG7-Ag and COX-2 in prediction of advances in gastric precancerous lesions.Material and methods:1.Samples collection501 gastric mucosal biopsies were collected from patients with gastric precancerous lesions(334), superifcial gastritis(59), atrophic gastritis(67), gastric cancer(41) from the Fourth Military Medical University, Tianjing Medical University and Shandong Medical University. 107 patients were followed up for more than one year. According to the dynamic histology, 107 cases were divided into two groups including advanced group(intestinal metaplasia→dysplasia, dysplasia→gastric cancer) and inadvanced group(intestinal metaplasia→intestinal metaplasia, dysplasia→dysplasia).2.Methods1) MG7 hybridoma cells were defrosted and cultured for MG7-Ab preparation.2) Immunohistochemistry was performed by using mouse monoclonal antibody to MG7-Ag and COX-2.Results1. Expression of MG7 antigen and COX-2 in precancerous gastric mucosal tissues.MG7-Ag was mainly located in the cell membrane and cytoplasm. COX-2 was mainly stained in the cell membrane and cytoplasm too.The expression of MG7-Ag and COX-2 was not significantly correlated with age and gender of patients with different precancerous gastric mucosal tissues (P>0.05). The positive rates of MG7-Ag and COX-2 expression were increased gradually with the development of gastric cancer lesions, and the difference was significant (P<0.05).In gastric precancerous tissues (including intestinal metaplasia and dysplasia), the expression of MG7-Ag and COX-2 was significantly higher than that in chronic gastritis (including superficial gastritis and atrophic gastritis). The positive rates of MG7 antigen and COX-2 was also increased gradually (P<0.05) in superficial gastritis,atrophic gastritis, intestinal metaplasia , dysplasia and gastric cancer.2. Correlation between expression of MG7-Ag and COX-2 in gastric precancerous tissues.Among the 334 patients with gastric precancerous lesions there were 39.2% with both MG7 antigen and COX-2 positive expression, and 33.5% with both negative. In MG7-Ag positive specimens, the positive rate of COX-2 expression was 79.9%. But in COX-2 positive specimens, the positive rate of MG7-Ag expression was 69.3%. The expression of MG7-Ag had a positive correlation to that of COX-2 in gastric precancerous tissues (P<0.05).3. Cancer prediction by combined detection of MG7-Ag and COX-2 in gastric precancerous lesion.Combined detection showed that the positive rates of MG7-Ag and COX-2 expression in advanced group were significantly higher than those in inadvanced group.When compared the expression of combined detection of MG7-Ag and COX-2 in advanced group and inadvancement group, we found for MG7(+) COX-2(+)/ MG7(-) COX-2(-) subtype the OR was 22.7, with the 95%CI 5.9—74.4(P<0.005). That is to say, MG7(+) COX-2(+) double positive indicated that the risk of precancerous progression increased significantly to over 22 times. There was a significant difference in precancerous progression between the MG7(+) COX-2(+) group and MG7(-)COX-2(-) group or between the MG7(+) COX-2(-) group and MG7(-)COX-2(-) group respectively (P<0.005). However, there was no significant difference between the MG7(-) COX-2(+) group and the MG7(-)COX-2(-) group (P>0.1).Conclusions:We successfully detected the gastric cancer-associated antigen MG7 in gastric precancerous lesions and its correlation with expression of COX-2. In our study, from intestinal metaplasia, low-moderate grade dysplasia to high grade dysplasia, expression of MG7-Ag and COX-2 was increased gradually. The positive rates of MG7 antigen and COX-2 expression in superficial gastritis,atrophic gastritis, intestinal metaplasia, dysplasia and gastric cancer also increased gradually. It indicated that MG7 antigen and COX-2 could be used as predictive factors of cancer development from gastric precancerous lesions. There is a positive correlation between the expression of MG7 antigen and COX-2 in gastric precancerous.Combined detection of MG7-Ag and COX-2 in followed-up patients, double positive staining in gastric precancerous lesions had an increased risk of precancerous progression over 22 times, which implys its great value of prediction of early gastric cancer from precancerous lesions.