A Study On Relationship Between Expression Of COX-2, P53 And MMP-2 And Carcinogenesis And Progression Of Human Gastric Adenocarcinoma

Background and aims:Gastric carcinoma(GC) is one of the most common malignant neoplasms in the digestive system, which heavily threats human being. Though studies on GC have lasted for about half century,no great progress was made. The main reason for death is invasion and metastasis of tumor. The problem researchers concentrated on is how to diagnose GC in early stage and monitor its invasion and metastasis.With the development of studies on GC,more and more people focused on cyclooxygenase-2(COX-2).COX-2 was found through epidemiological investigation.Researchers found that the incidence of colorectal cancer can be reduced to from forty to fifty per cent through consecutive adiministering nonsteroidal anti-inflammatory drugs(NSAIDs).It is a key enzyme in the process of prostaglandins'synthasis, which can be inhibited by NSAIDs. Studies show that COX-2 might play a important role in the carcinogenesis and progression of tumor. The overexpression of COX-2 in gastric mucosa may be a early event in the process of carcinogenesis. So it can be considered as an index to detect carcinogenesis.Matrix metaIloproteinase-2(MMP-2) is one of members in MMPfamilies.lt plays a critical role in the process of degenerating extracellular membrane(ECM) mediated by tumors. Studies had shown that COX-2 could promote invasion and metastasis of tumor by upregulating the expression of MMP-2. As a result of that,MMP-2 overexpressed in tumors with metastasis.P53 is one of suppression genes founded in 1980s which is related to carcinogenesis and progression of tumors.Many studies related to p53 had been done for many years.However studies related to the relationship about COX-2,P53 and MMP-2 had not been reported.This study discusses the expression of the three factors in gastric adenocarcinoma , which aims to analyze its' effects on GC carcinogenesis and progression and the relation between each other. Materials and Methods: 61 cases of gastric carcinoma specimen,paracarcinoma tissues and normal gastric mucosa specimen were collected.All the tissues were fixed in 10% neutral formalin and embedded in paraffin. Immunohistochemical streptavidin peroxidase conjugate method was used to analyse COX-2, P53 and MMP-2 expression in normal gastric mucosa(NGM),chronic atrophic gastritis(CAG)with metaplasia, dysplasia and gastric carcinoma. Statistical analysis was performed with SPSS 11.0 software,using Spearman correlation analysis,Kruskal-Wallis Test,Chi-squre and Fisher's exact probability test. Statistically significant level was considered as "alpha=0.05". Results:1.Cox-2 expression was mainly observed in the cytoplasm.MMP-2 expression was mainly observed in the cytoplasm and/or on the membrane of cells.The positive staining of p53 located in the nuleus. There are three types in the distribution of positive cells.The first type is sporatic distribution. Single positive cell can only be seen. The second is spottedly distributed. The positive cells collected in some regions of epithelial or carcinoma tissues.The third type is diffuse distribution. Almost all the cells in lesion were stained, which can be seen in the three indexes. There were positive expression .negative expression and different expression degree in the same carcinoma tissue.2.COX-2 and P53 didn't expressed in the normal gastric mucosa,but MMP-2 had aslight expression in it. The positive rate of MMP-2 was 8.3 % ( 1/11) .The positive rateof COX-2 in CAG with metaplasia, dysplasia and GC was 41.2%(7/17), 46.2%(12/26),78.7% (48/61) respectively. The positive rate of p53 in CAG withmetaplasia,dysplasia and GC was 35.3% (6/17), 38.5% (10/26), 63.9% (39/61) respectively. The positive rate of MMP-2 in CAG with metaplasia, dysplasia and GC was 17.6%(3/17), 46.2% (12/26), 68.9% (42/61) respectively. The three indexes'positive expression in GC had a significant difference compared with NGM,CAG with metaplsia and dysplasia.3. The positive rates of COX-2,P53 and MMP-2 in lymphnode metastasis group were 84.4% (27/32), 72.4% (21/29); 90.6%(29/32), 3...