Expression Of COX-2 And MMP-9 In Gastric Carcinoma And Its Correlation With Angiogenesis And Biologic Behaviors Of Tumor

Background: Cyclooxygenase (COX) is a rate-limiting enzyme in the conversion of arachidonic acid(AA)to prostaglandins(PGs). Two isoforms of COX, COX-1 and COX-2, have been identified. COX-2 is inducible and low or undetectable in most tissues but can be highly induced in response to cell activation. Matrix metalloproteinases (MMPs), zinc dependent proteolytic enzymes, can cleave extracellular matrix (ECM). Matrix metalloproteinase-9 is one of the important members of MMPs, which can degrade collagen Ⅳ, collagenV and gelatine of ECM. Studies have shown overexprssion of COX-2 and MMP-9 are significantly correlated with tumor growth and progression but about their exact mechanism in carcinogenesi are yet not distinct. Angiogenesis is essential for tumor growth and progression and it maybe an important pathways for COX-2 and MMP-9 in carcinogenesis.Objective: To investigate the expression of COX-2 and MMP-9 in gastric carcinoma and their correlation with angiogenesis and biologic behaviors of tumor. Methods: Ninty-six resected specimens of patients undergoing surgery for primary gastric carcinoma were collected and thirty paracancerous tissues were also collected as the control. Immunohistochemical stain was used for detecting the expression of COX-2 and MMP-9. Monoclonal antibody against CD34 was used for displaying vascular endothelial cells, and microvascular density (MVD) was examinated by counting of CD34-positive vascular endothelial cells. Results: 1) The positive expression rates of COX-2 and MMP-9 in gastric carcinoma were 80.2% and 74.0% respectively, and MVD averaged 32.5 ± 8.3, which were significantly higher than those in the control (13.3%,10.0%,13.1±2.4; P<0.01). 2) The positive expression rates of COX-2 and MMP-9 in 58 cases with lymph node metastasis were 87.9% (51/58), 82.7% (48/58) respectively and MVD was 35.0±8.5, which were higher than those in the cases without lymph node metastasis (68.4%, 60.5%, 28.7±6.8; P<0.05 or P<0.01). Furthermore, COX-2 and MMP-9 expression and MVD were associated with depth of tumor invasion (P<0.05 or P<0.01), but negative correlated to age, gender, tumor position, cellular differentiation and histologic type (P>0.05). 3) COX-2 expression were positively correlated to MVD (r = 0.311, P<0.01). MMP-9 expression were also positively correlation to MVD (r = 0.349,P<0.01). 4) Postive co-expression of COX-2 and MMP-9 was detected in 59.6% specimens of gastric carcinoma and expression of COX-2 was rightly correlated to MMP-9 expression (r = 0.244, P<0.05). MVD in the specimens with COX-2 and MMP-9 co-expression was significantly higher than those without co-expression (34.9±8.3 vs 29.1±7.5, P<0.01). In addition, co-expression of COX-2 and MMP-9 was significantly related with invasion depth of tumor and lymph node metastasis in gastric carcinoma (P<0.01).Conclusions: The present study demonstrates that overexpression of COX-2 and MMP-9 is related to tumor invasion and lymph node metastasis in gastric carcinoma. COX-2 and MMP-9 expression are highly correlated with MVD. These results provide evidence that angiogenesis plays an important role for COX-2 and MMP-9 in carcinogenesis.