乳腺癌淋巴管生成与血管内皮生长因子-C、环氧化酶-2表达的关系

Coexpression of VEGF-C and COX-2 and its association with lymphangiogenesis and prognosis in human breast cancer

目的探讨血管内皮生长因子(VEGF)-C、环氧化酶(COX)-2在乳腺癌组织中的相互表达关系及与淋巴管生成和预后的关系。方法应用免疫组织化学法检测70例乳腺癌组织COX-2与VEGF-C蛋白的表达,并用淋巴管内皮细胞特异性抗体D2-40标记淋巴管,计数肿瘤淋巴管密度(LVD),结合临床病理特征和随访资料进行分析。结果(1)乳腺癌组织COX-2、VEGF-C高表达率分别为65.7%(46/70)和42.8%(30/70)。COX-2与VEGF-C蛋白表达之间存在显著相关(r=0.529,P<0.01)。(2)COX-2蛋白的高表达与淋巴结转移、LVD和淋巴管浸润呈正相关(P<0.05),与雌激素受体状态、无病生存率和总生存率呈负相关(P<0.05)。VEGF-C蛋白的高表达与淋巴结转移、LVD、淋巴管浸润呈正相关(P<0.05),与组织学分化、无病生存率和总生存率呈负相关(P<0.05)。结论COX-2可能通过上调VEGF-C表达来促进乳腺癌淋巴管生成,从而导致淋巴结转移的发生。COX-2和VEGF-C的高表达提示乳腺癌患者容易出现淋巴结转移和预后不良。

Objective To investigate the relationship between vascular endothelial growth factor- C （VEGF-C） and cyclooxygenase-2 （COX-2） in human breast cancer, and their correlations with lymphangiogenesis and prognosis. Methods Tissue samples of breast cancer from 70 patients were immunohistochemically examined for the expression of VEGF-C, COX-2 and D2-40. The association between COX- 2 and VEGF-C expression and clinicopathological parameters and prognosis were analysised. Results Elevated VEGF-C expression was observed in 30 of 70 patients （42.8%） ,while elevated COX-2 expression occurred in 46 of 70 tumor samples （65.7%）. A significant correlation was found between the expression of VEGF-C and COX-2 （r = 0. 529 ,P 〈 0.01 ）. High expression of both the VEGF-C and COX-2 was correlated with the lymph node metastasis, lymph vessel density and D2-40 positive lymph vessel invasion （P 〈 0.05 ）. Additionly, high expression of VEGF-C, but not COX-2 was correlated with advanced histological grading （ P 〈 0.01 ）. Univariate analysis demonstrated that high expression of both VEGF-C and COX- 2 was associated with worse disease free survival （ P 〈 0.01 ） and overall survival （ P 〈 0.05 ）. Conclusion VEGF-C and COX-2 are coexpressed and significantly associated with lymphangiogenesis and prognosis in breast cancer, suggesting COX-2 may up-regulate VEGF-C expression and thus promote lymph node metastasis via lymphangiogenesis pathway in human breast cancer.