Involvement of cyclooxygenase-2 and vascular endothelial growth factor in vascularization and lymph node metastasis of colorectal cancers with submucosal invasion

Background and Aims: Although patients with early colorectal cancer invading the submucosa (CRC-sm) may be treated with endoscopic mucosal resection alone, they generally undergo additional surgery because of the risk of lymph node metastasis. The aims of the present study were to examine the roles of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in tumor vascularization and to investigate whether COX-2 and VEGF expression and tumor vascularity are useful markers for predicting lymph node metastasis in CRC-sm. Methods: Twenty-seven resected specimens of CRC-sm with lymph node dissection were examined, and expression of COX-2 and VEGF was evaluated immunohistochemically and scored. Microvessel density (MVD) in CRC-sm tissues was estimated using a Macscope system after CD34 immunostaining. The relationships among clinicopathological parameters, COX-2 and VEGF expression, and MVD in CRC-sm tissues were then analyzed. Results: Scores for COX-2, VEGF and MVD were all significantly higher in patients with CRC-sm with lymphatic invasion or lymph node metastasis. COX-2 score (P < 0.0001) and VEGF score (P = 0.035) were significantly correlated with MVD in CRC-sm tissues. In addition, COX-2 score was significantly correlated with VEGF score in the CRC-sm specimens examined. Conclusions: Both COX-2 and VEGF are involved in tumor vascularization in CRC-sm. COX-2 expression, VEGF expression, and MVD are possible markers for predicting lymph node metastasis in patients with CRC-sm, and use of COX-2 expression may be clinically practical.