宫颈癌中iNOS的表达与肿瘤新生淋巴管及VEGF-C的关系

目的:探测人宫颈癌中的诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)、血管内皮生长因子-C(vascular endothelial growth factor,VEGF-C)的表达与D2-40标记的淋巴管密度的关系.方法:采用免疫组化SP法检测宫颈鳞状细胞癌中iNOS、VEGF-C的表达情况,并用D2-40进行癌组织淋巴管染色,测定其淋巴管密度(lymphatic vessel density,LVD),另取正常宫颈组织10例作对照,观察上述因子在宫颈癌及正常宫颈中的表达及其与肿瘤病理参数之间的相关性.结果:与正常宫颈组织相比,宫颈癌组织中具有更高的iNOS、VEGF-C的表达率及淋巴管密度(t=2.39、3.08,P=0.021、0.003).与无淋巴结转移组相比,淋巴结转移组具有更高的iNOS、VEGF-C阳性表达率(P =0.044、0.035)及淋巴管密度(t=3.79,P＜0.001);iNOS、VEGF-C阳性共表达与肿瘤淋巴结转移之间存在正相关(P=0.046),宫颈癌组织中iNOS、VEGF-C的表达具有相关性(P＜0.001).结论:iNOS、VEGF-C在宫颈癌组织中呈过表达,其与宫颈癌的淋巴转移关系密切;iNOS可能通过催化产生NO上调VEGF-C的表达,诱导肿瘤淋巴管生成,导致宫颈癌的淋巴道转移.iNOS、VEGF-C均参与宫颈的发展、浸润和转移,可作为评估宫颈癌的生物学行为和判断预后的指标.针对iNOS、VEGF-C的靶向治疗可成为宫颈癌治疗的新靶点.

Inducible nitric oxide synthase activity correlates with lymphangiogenesis and vascular endothelial growth factor-C expression in cervical cancer

Objective:To explore the role of iNOS(inducible nitric oxide synthase) and VEGF-C (vascular endothelial growth factor-C) in the lymphatic signal transduction pathway,with a goal to provide new targets for the treatment of cervical cancer.Methods:Tissue sections from 65 patients (55 cervical squamous cell carcinoma,10 normal cervical tissues) were examined immunohistochemically(SP method) for protein expression of iNOS and VEGF-C.LVD(lymphatic vessel density) was counted by endothelial cells immuno-stained by D2-40 antibody.Results:The expression of iNOS,VEGF-C and LVD in cervical cancer were higher than normal cervical tissue,the difference was significant.Also,the expression of iNOS and VEGF-C had positive correlation with lymph node metastasis (P ＜ 0.05).The LVD in tumors were higher in the groups in which iNOS/VEGF-C were positive staining(P =0.044,0.035).Also,LVD had positive correlation with lymph node metastasis(P ＜0.01).Conclusion:The expressions of iNOS and VEGF-C were associated with LVD,which indicated that they can promote tumor lymphatic metastasis.iNOS may induce the expression of VEGF-C by catalyzing NO production,induce lymphangiogenesis and lead to the lymphatic metastasis of cervical cancer.iNOS and VEGF-C are involved in the development,infiltration and metastasis of cervical cancer,so iNOS and VEGF-C can be served as prognostic factors for patients with cervical cancer.