Cyclooxygenase-2 expression is associated with VEGF-C and lymph node metastases in gastric cancer patients

Previous studies have suggested that cyclooxygenase-2 (COX-2) over-expression is associated with angiogenesis in gastric cancer. However, the relationship between COX-2 and lymphangiogenesis is still unclear. The aim of this study was to determine the relationship between COX-2 expression and lymphangiogenic factor, vascular endothelial growth factor-C (VEGF-C), in human gastric cancer, as well as to correlate with clinicopathological parameters. Sixty-three gastric cancer patients underwent radical gastrectomy (D2 or D3) were enrolled in this study. The expression of COX-2 and VEGF-C were detected by immunohistochemistry, and the small lymphatic vessels were immunohistochemically stained by LYVE-1 antibody. The association between COX-2 and VEGF-C expressions and clinicopathological parameters (such as gender, tumor location, lymph node status and Lauren classification) were determined. VEGF-C over-expression was observed in 33 of 63 patients (52%), while COX-2 over-expression occurred in 42 of 63 tumor samples (67%). Presence of microlymphatic vessels with LYVE-1 staining was found in 35 cases. COX-2 over-expression was highly correlated with VEGF-C over-expression (P = 0.032), microlymphatic vessels (P = 0.002) as well as presence of metastatic lymph nodes (P = 0.007). However, no significant correlation was found between COX-2 expression and other clinicopathological parameters. Our data suggest that COX-2 expression is associated with lymphangiogenesis and lymph node metastasis in human gastric carcinoma. This raises the possibility that COX-2-mediated VEGF-C over-expression might promote lymph node metastasis via lymphangiogenesis pathway in patients with gastric cancer.