Expressions of COX-2 and VEGF-C in gastric cancer: correlations with lymphangiogenesis and prognostic implications

Using immunohistochemistry, COX-2, VEGF-C and level of LVD were analyzed in 56 R0-resected primary gastric adenocarcinomas, while paracancerous normal mucosal tissues were also collected as control from 25 concurrent patients. The relationships among COX-2 and VEGF-C expression, LVD, and clinicopathologic parameters were analyzed. The correlations of COX-2, VEGF-C and level of LVD with patient prognosis were also evaluated by univariate tests and multivariate Cox regression.The expression rates of COX-2 and VEGF-C were 69.64% and 55.36%, respectively, in gastric carcinoma. Peritumoral LVD was significantly higher than that in both normal and intratumoral tissue (P < 0.05). It was significantly correlated with lymph node metastasis and invasion depth (P = 0.003, P = 0.05). VEGF-C was significantly associated with peritumoral LVD (r = 0.308, P = 0.021). However, COX-2 was not correlated with VEGF-C (r = 0.110, P = 0.419) or LVD (r = 0.042, P = 0.758). Univariate analysis showed that survival time was impaired by higher COX-2 expression and higher peritumoral LVD. Multivariate survival analysis showed that age, COX-2 expression and peritumoral LVD were independent prognostic factors.Although COX-2 expression was associated with survival time, it was not correlated with VEGF-C and peritumoral LVD. Our data did not show that overexpression of COX-2 promotes tumor lymphangiogenesis through an up-regulation of VEGF-C expression in gastric carcinoma. Age, COX-2 and peritumoral LVD were independent prognostic factors for human gastric carcinoma.Gastric carcinoma is one of the most common digestive malignancies in the world, especially in East and Southeast Asia, including China [1]. Regional lymph nodes are the most common site of metastasis while lymph node metastasis is a major prognostic factor in gastric carcinomas. Understanding the mechanisms of lymphatic metastasis represents a crucial step and may result in a new therapeutic target in the treatment of human cancer. L