Clinic Significance And Correlation Among COX-2,VEGF-C, Formation Of Lymph Vessel And Blood Vessel

Background and Purpose: Gastric carcinoma is one of the most common malignancies of the digestive tract. Blood and lymph node metastasis are the most important factors for the recurrence and survival of gastric carcinoma patients. The mechanism of tumor angiogenesis and anti-angiogenesis treatment has been widely researched . But the mechanism of tumor lymphangiogenesis and lymph node metastasis is still unclear. Many studies indicate that vascular endothelial growth factor-C (VEGF-C)can promote lymphangiogenesis and lymph node metastasis. The VEGF-C are found that it highly expresses and relates to lymph node metastasis in many tumor. The role of VEGF-C in gastric carcinoma remains uncleare and the correlation between VEGF-C and microlymphatic density,lymph node metastasis,prognosis of gastric carcinoma are conficting in the published literature. Cyclooxygenase(COX-2) is the rate-limiting enzyme in prostaglandin synthesis. The over-expression of COX-2 has been found in many malignant tumors and Cox-2 may relates to carcinogenesis, development and metastasis of tumor. Several lines of experimental evidence indicated that over-expression of vascular endothelial growth factor-C and cyclooxygenase-2 promotes angiogenesis and lymphangiogenesis. Our study were designed to examine the expression of COX-2,VEGF-C protein and the MLD,MVD in human gastric carcinoma using immunohistochemical method and evaluate their correlations each other and their correlations with clinicopathological characteristics and prognosis of gastric cancer patients.Materials and methods: Tissue samples of primary tumors from 56 patients with gastric carcinoma who undergo curative surgical resections were immunohistochemically examined for vascular endothelial growth factor-C, cyclooxygenase-2, and D2-40, CD34 expressions. 25 paracancerous tissues were examined as control. Then, we used SPSS software to analyze their relationships and correlations with clinicopathologic characteristics and patients' survival timeResults:1. The high expression rate of COX-2 was 69.64% in gastric carcinoma and significantly increased compared with that in paracancerous tissues. The positive expression rate of VEGF-C was 55.36%. The expression rate of VEGF-C, COX-2 in different tumor differentiation ,invasive depth ,lymph node matastasis ,stage groups has no statistical significance(P>0.05) .2. The numbers and morph of the lympgatic vessel in tumor borderline tissue,tumor center tissue and paracancerous normal tissue of gastric carcinoma are different: The MLD immunostained with D2-40 in tumor borderline tissue of gastric carcinoma was higher than that in the paracancerous normal tissue and tumor center tissue (P<0.05) . The Spearman rank correlation test showed the tumor borderline MLD was related with the depth of invasion(r= 0.274 ,P=0.041 ),lymph node metatasis(r=0.501,p<0.001 )and clinical stage(r=0.413,P=0.002).The MVD in tumor tissue was higher than that in the paracancerous normal tissue (P<0.05) . The tumor MVD had no statistics significances in different clinicopathologic characteristics groups(P>0.05).3. The tumor borderline MLD was significantly higher in VEGF-C positivegroup than in VEGF-C negative group and there is positive correlation between the expression of VEGF-C and tumor borderline MLD (r=0.308,P<0.05). The tumor MVD was significantly higher in patients with high COX-2 expression than in those low expression (P<0.001). There is positive correlation between COX-2 and gastric carcimoam MVD (r=0.516,P<0.001); There are no correlations between COX-2 and VEGF-C , VEGF-C and MVD , COX-2 and MLD (P>0.05) .4. The analysis of prognosis related factors:The survival time of patients withCOX-2 high expression tumors was significantly shorter than that of patients with COX-2 low expression tumors(P=0.026). The survival time of patients had no significantly difference between VEGF-C positeve tumors with VEGF-C negative tumors(P>0.05).High tumor borderline MLD(R=-0..347, P<0.05) and tumor MVD (R=-0.302, P<0.05)was associated with worse overall survival.When multivariate Cox regression model was applied, tumor MVD and clinic stage were independent prognostic factors for mortality of these patients. Conclusion:1. The over-expression of COX-2 was found in gastric carcinoma . The 5-year survival rate of gastric carcinoma was shorter when COX-2 was highly expressed.2. The MLD in tumor borderline of gastric carcinoma was higher than that in the paracancerous normal tissue and tumor center tissue. The tumor borderline MLD was related with the depth of invasion,lymph node metatasis and clinical stage. High tumor borderline MLD was associated with worse overall survival. These results indicate that lyphangiogesis of tumor borderline tissue relates to lymph node metastasis.3. The MVD in tumor tissue was higher than that in the paracancerous normal tissue, high tumor MVD was associated with worse overall survival.4. There is positive correlation between COX-2 and gastric carcimoam MVD and COX-2 and MVD are indexes to reflect the angiogenesis of gastreic carcinoma. There is positive correlation between VEGF-C and tumor borderline MLD of gastric carcinoma and VEGF-C and tumor borderline MLD are indexes to reflect the lymphangiogenesis of gastreic carcinoma.5. Tumor MVD and clinic stage were independent prognostic factors for mortality of gastric carcinoma.