Expression of Matrix Metalloproteinase-9 mRNA and Vascular Endothelial Growth Factor Protein in Gastric Carcinoma and its Relationship to its Pathological Features and Prognosis

To investigate matrix metalloproteinase-9 (MMP-9) mRNA and vascular endothelial growth factor (VEGF) protein expression in gastric carcinoma and its correlation with microvascular density, growth-pattern, invasion, metastasis, and prognosis. In situ hybridization of MMP-9 mRNA and immunohistochemistry of VEGF and CD34 proteins were performed on surgical specimens of gastric cancers from 118 patients compared with 20 nonmalignant gastric mucosae. Their relationships to pathological parameters and survival times were determined by statistical analysis. The positive rate of MMP-9 in noncancerous gastric mucosae was significantly lower than that of gastric cancer tissue (60.17%, P < 0.01). In patients with cancers of the infiltrating type, at stage T3-T4, with vessel invasion, lymphatic metastasis, hepatic, or peritoneal metastasis, the positive expression rates of MMP-9 mRNA, VEGF protein, and CD34 were significantly higher than those for patients with tumors of the expanding type (P < 0.01), at stage T1-T2 (P < 0.01), with nonvessel invasion (P < 0.05), without lymphatic metastasis (P < 0.05), and without hepatic (P < 0.001) or peritoneal metastasis (P < 0.001), respectively. Expression of MMP-9 mRNA was positively related to that of VEGF protein (P < 0.001) and microvascular density (P < 0.001). Patients with higher MMP-9 mRNA and VEGF expression demonstrated vivid tumor angiogenesis and poor 5-year survival rate. MMP-9 and VEGF expression is associated with enhanced tumor angiogenesis and may play crucial roles in the invasion and metastasis of gastric carcinoma. Therefore, MMP-9 and VEGF may represent prognostic biomarkers and promising targets for therapeutic intervention. Anat Rec, 293:2012-2019, 2010. (C) 2010 Wiley-Liss, Inc.