COX-2 和 VEGF-C 在胃癌中的表达：与淋巴管生成的相关性及其预后意义。

BACKGROUND

Cyclooxygenase-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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

背景

环氧化酶-2（COX-2）最近被认为通过上调乳腺癌和肺癌中的血管内皮生长因子-C（VEGF-C）来促进淋巴管生成。然而，COX-2 对胃癌淋巴管生成的影响尚不清楚。本研究旨在检测 COX-2 和 VEGF-C 在人胃癌中的表达，并分析其与淋巴管密度（LVD）、临床病理特征和生存预后的相关性。

方法

采用免疫组织化学法，分析 56 例 R0 切除的原发性胃腺癌中 COX-2、VEGF-C 和 LVD 水平，同时收集 25 例同期患者的癌旁正常黏膜组织作为对照。分析 COX-2 与 VEGF-C 表达、LVD 与临床病理参数之间的关系。采用单因素检验和多因素 Cox 回归分析 COX-2、VEGF-C 和 LVD 水平与患者预后的关系。

结果

胃癌中 COX-2 和 VEGF-C 的表达率分别为 69.64%和 55.36%。肿瘤旁 LVD 明显高于正常和肿瘤内组织（P<0.05）。与淋巴结转移和浸润深度显著相关（P=0.003，P=0.05）。VEGF-C 与肿瘤旁 LVD 显著相关（r=0.308，P=0.021）。然而，COX-2 与 VEGF-C（r=0.110，P=0.419）或 LVD（r=0.042，P=0.758）均无相关性。单因素分析表明，COX-2 高表达和肿瘤旁 LVD 高与生存时间受损有关。多因素生存分析显示，年龄、COX-2 表达和肿瘤旁 LVD 是独立的预后因素。