诱导型一氧化氮合酶、环氧合酶-2与乳腺癌淋巴管生成的关系及其临床意义

Relationships between inducible nitric oxide synthase,cyclooxygenase-2 and breast cancer lymphangiogenesis and clinical significance

目的探讨诱导型一氧化氮合酶(iNOS)和环氧合酶-2(COX-2)在乳腺癌间质淋巴管生成中的作用机制及其临床意义。方法收集乳腺浸润性导管癌组织90例和乳腺纤维腺瘤组织30例,应用寡核苷酸探针原位杂交法检测组织中iNOS和COX-2的mRNA表达,另以Elivision免疫组化法检测淋巴管内皮细胞透明质酸受体1(LYVE-1)和血管内皮生长因子-C(VEGF-C)蛋白的表达情况,分析iNOS和COX-2与LYVE-1标记的淋巴管密度(LVD)以及VEGF-C的关系。结果在90例乳腺癌中iNOS、COX-2的mRNA阳性率分别为66.7%、68.9%,LVD为(8.03±2.26)个/HPF,VEGF-C表达阳性率为47.8%,与良性对照组比较均有显著差异(P<0.01)。iNOS mRNA表达与乳腺癌肿瘤大小、分期、LVD和VEGF-C表达呈正相关(P<0.01);COX-2 mRNA表达与肿瘤分级、淋巴结转移、分期和LVD呈正相关(P<0.05),与VEGF-C表达无显著相关(P>0.05);iNOS和COX-2的mRNA阳性表达呈正相关(P<0.05)。结论 iNOS和COX-2具有协同促进乳腺癌淋巴管生成及侵袭转移的作用,有望在乳腺癌的临床预后判断及靶向治疗中发挥作用。

Objective To study the role and mechanism of inducible nitric oxide synthase（iNOS） and cyclooxygenase-2（COX-2） in breast cancer tissues stroma lymphangiogenesis and their clinical significance.Methods Tissues were obtained from 90 patients with breast invasive ductal cancer and 30 with breast fibroadenoma.The mRNA expressions of iNOS and COX-2 were examined by in situ hybridization with oligonucleotide probe,the protein expression of lymphatic vessel endothelial hyaluronan receptor 1（LYVE-1） and vascular endothelial growth factor-C（VEGF-C） were examined by Elivision immunohistochemistry.Relationships between iNOS,COX-2 and LYVE-1-labeled lymphatic vessel density（LVD）,VEGF-C were analyzed.Results In 90 cases of breast cancer,the mRNA expression positive incidences of iNOS and COX-2 were respectively 66.7%,68.9%,the LVD was（8.03±2.26）/HPF,the expression positive incidences of VEGF-C was 47.8%,which all differentiated apparently than those of the benign control group（P0.01）.In breast cancer tissues,the expression of iNOS mRNA was positively related to tumor size,clinical stage,LVD and VEGF-C（P0.05）.The expression of COX-2 mRNA was positively related to histopathologic grade,lymphnode metastasis,clinical stage and LVD（P0.05）,but unapparently related to VEGF-C expression（P0.05）.In breast cancer tissues,the iNOS mRNA positive expression was positively related to COX-2（P0.05）.Conclusions iNOS and COX-2 may synergicly promote the lymphangiogenesis,invasion and metastasis of breast cancer.It is hopeful that iNOS and COX-2 play roles in prognosis judgement and targeted therapy of breast cancer.