摘要目的 探讨环氧合酶-2(COX-2)对人乳腺癌淋巴管形成的影响.方法 1998年11月至2002年3月行手术治疗并经病理证实的乳腺癌患者94例,随访83例,失访11例.免疫组织化学方法 检测COX-2、血管内皮生长因子-C(VEGF-C)及D2-40在乳腺癌中的表达.逆转录聚合酶链式反应(RT-PCR)和Western印迹法分别检测加入不同浓度COX-2抑制剂尼美舒利后VEGF-C mRNA及蛋白的变化.Western印迹法检测加入外源性前列腺素E2(PGE2)和曲妥珠单抗后VEGF-C蛋白的变化.结果 46.8%的乳腺癌组织呈COX-2高表达,51.1%呈VEGF-C高表达.COX-2与VEGF-C(P＜0.01)、淋巴管密度(P=0.032)和淋巴结转移(P=0.035)呈正相关,与乳腺癌患者的无病生存率(P=0.010)和总生存率(P=0.040)呈负相关.尼美舒利以剂量依赖性方式下调VEGF-C mRNA及蛋白表达,而PGE2上调其蛋白表达.曲妥珠单抗可显著降低VEGF-C的蛋白表达.结论 COX-2可通过上调VEGF-C的表达,促进乳腺癌的淋巴管形成和淋巴结转移,并影响乳腺癌患者的预后.

abstractsObjective To study the effect of cyclooxygenase-2(COX-2)on lymphangiogenasis in breast cancer.Methods By the means of immunohistochemistry,COX-2,vascular endothelial growth factor-C(VEGF-C)and D2-40 were examinated in the tissue samples of primary tumors from 94 patients underwent snrgical resections for breast cancer from November 1998 to March 2002.Eighty-three patients were followed-up.The expressions of VEGF-C mRNA and protein were detected by reverse transcription polymerase chain reaction(RT-PCR)and Western blot in MDA-MB-231 cell lines by the treatment of selective COX-2 inhibitor Nimesulide at different doses.The expressions of VEGF-C protein were evaluated in MDA-MB-231 cells treated by PGE2(1 μg/ml)and Trastuzumab(1 μg/ml),respectively.Results COX-2 over-expression was observed in 46.8%of surgical specimens(44/94),while VEGF-C overexpression occurred in 51.1%of tumor samples(48/94).COX-2 was strongly correlated with VEGF-C expression(P＜0.01),microlymphatic vessels(P=0.032)and metastatic lymph nodes(P=0.035).Patients with COX-2 positive tumors had a significant shorter survival time than those with negative tumors did,including disease-free survival(P=0.010)and overall survival(P=0.040).Nimesulide could downregulate the expressions of VEGF-C mRNA and protein in a does-dependent manner,while PGE2 could upregulate the expressions.The expression of VEGF-C protein up-regulated by PGE2 treatment was decreased by Trastuzumab.Conclusions COX-2 over-expression can up-regulate the expression of VEGF-C.VEGF-C might promote lymph node metastasis by a lymphangiogenic pathway,then affect the prognosis of the patients with breast cancer.