Abstract
BackgroundCyclooxygenase-2 (COX-2) has recently been considered to promote lymphangiogenesis by up-regulating vascular endothelial growth factor-C (VEGF-C) in breast and lung cancer. However, the impact of COX-2 on lymphangiogenesis of gastric cancer remains unclear. This study aims to test the expression of COX-2 and VEGF-C in human gastric cancer, and to analyze the correlation with lymphatic vessel density (LVD), clinicopathologic features and survival prognosis.MethodsUsing 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.ResultsThe 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.ConclusionsAlthough 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.
Highlights
Cyclooxygenase-2 (COX-2) has recently been considered to promote lymphangiogenesis by upregulating vascular endothelial growth factor-C (VEGF-C) in breast and lung cancer
Padera et al have reported that tumor cells are not able to metastasis by intratumoral lymphatic vessels [2], but other studies have demonstrated that the presence of intratumoral lymphangiogenesis and intratumoral lymphatic vessel density (LVD) are correlated with lymph node metastasis and prognosis in several tumors [36,37,38]
Though COX-2 expression was associated with survival time, COX-2 was not correlated with VEGF-C or LVD
Summary
Cyclooxygenase-2 (COX-2) has recently been considered to promote lymphangiogenesis by upregulating vascular endothelial growth factor-C (VEGF-C) in breast and lung cancer. This study aims to test the expression of COX-2 and VEGF-C in human gastric cancer, and to analyze the correlation with lymphatic vessel density (LVD), clinicopathologic features and survival prognosis. Understanding the mechanisms of lymphatic metastasis represents a crucial step and may result in a LVD of cancer tissue has been considered one of the prognostic factors for survival outcome in various cancers including gastric carcinoma [6,7]. It has been found that VEGF-C is strongly expressed and has become an important predictor of lymphangiogenesis and prognosis in numerous types of cancers, including gastric carcinoma [8,9,10]. VEGF-C can promote lymphangiogenesis and lymph node metastasis of tumors by activating its special receptor vascular endothelial growth factor receptor-3 (VEGFR-3) [11,12]
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