Clinicopathological significance of E-cadherin, VEGF, and MMPs in gastric cancer

Abstract

E-cadherin, vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs) are important molecules involved in tumor metastasis. In this study, we examined the expressions of E-cadherin, VEGF, MMP-1, MMP-2, and microvessel density (MVD), as well as microlymphatic vessel density (MLVD) in 200 cases of gastric cancer tissues, and determined the relationship between these parameters and the clinicopathological features and patient survival. Protein expressions, MVD, and MLVD were detected by immunohistochemistry. The correlation between the expression levels of these molecules and the clinicopathological features was analyzed. Patient survival was estimated by Kaplan and Meier analysis. Compared to normal gastric mucosa, expression of E-cadherin was reduced in 78% of gastric cancer tissues and 44.6% of adjacent non-cancerous gastric tissues. VEGF was positive in 81.5% of gastric cancer tissues, 35.7% of adjacent non-cancerous gastric tissues, and 10% of normal gastric mucosa. MMP-1 was positive in 80.5% of gastric cancer tissues, 69.6% of adjacent non-cancerous gastric tissues, and 20% of normal gastric mucosa. Reduced expression of E-cadherin was closely correlated with poor tumor differentiation and a deeper tumor invasion. Increased expressions of VEGF and MMP-1 were closely linked with poor differentiation and Lauren classification. Increased expression of MMP-2 was closely correlated with more lymph node metastasis, a deeper invasion, and a larger tumor size. More MVD was observed in VEGF-positive tissues than in VEGF negative tissues. Therefore, abnormal expressions of E-cadherin, VEGF, MMP-1, and MMP-2 are widely present in gastric cancer tissues. Abnormal expressions of E-cadherin, VEGF, and MMP-2 may represent the early molecular changes in the development of gastric cancer. Positive expression of E-cadherin and negative expression of VEGF and MMP-2 are correlated with a better patient survival.