Gli1蛋白和血管内皮生长因子-C在甲状腺乳头状癌中的表达及其与颈部淋巴结转移的关系
Gli1단백화혈관내피생장인자-C재갑상선유두상암중적표체급기여경부림파결전이적관계
Expression of Gli1 protein and vascular endothelial growth factor-C in papillary thyroid carcinoma and their relationship with cervical lymph node metastasis
  • 万方数据
    中国医师进修杂志 중국의사진수잡지
    CHINESE JOURNAL OF POSTGRADUATES OF MEDICINE
    2013年 20期 30-34 ,共5页

    石东亮%赵苏远%陈倩倩%李清怀

    석동량%조소원%진천천%리청부

    血管内皮生长因子C%甲状腺肿瘤%肿瘤转移 血管內皮生長因子C%甲狀腺腫瘤%腫瘤轉移
    혈관내피생장인자C%갑상선종류%종류전이
    Vascular endothelial growth factor C%Thyroid neoplasms%Neoplasm metastasis
    目的 研究Gli1蛋白和血管内皮生长因子(VEGF)-C在甲状腺乳头状癌中的表达及其与甲状腺乳头状癌临床病理特征和颈部淋巴结转移的关系.方法 采用免疫组织化学EnVision法测定67例甲状腺乳头状癌患者及32例结节性甲状腺肿患者病理组织标本中Gli1蛋白和VEGF-C的表达,同时分别用单克隆抗体CD34和D2-40标记各病理标本中的新生微血管和微淋巴管,计算肿瘤的微血管密度(MVD)和微淋巴管密度(MLVD),分析Gli1蛋白阳性表达与MVD的关系、VEGF-C阳性表达与MLVD的关系及其与颈部淋巴结转移的关系.结果 甲状腺乳头状癌组织中Gli1蛋白阳性率、VEGF-C阳性率、MVD、MLVD分别为67.16％ (45/67)、70.15％ (47/67)、23.14±2.06、13.36±1.32,结节性甲状腺肿组织中分别为43.75％(14/32)、31.25％(10/32)、2.14±0.31、3.53±0.65,两者比较差异有统计学意义(P＜0.05).Gli1蛋白阳性表达与患者的年龄、肿瘤大小有相关性(P＜0.05),而VEGF-C阳性表达与患者的年龄、肿瘤大小无相关性(P＞0.05).Gli1蛋白和VEGF-C在TNM分期Ⅲ～Ⅳ期甲状腺乳头状癌患者的阳性表达率显著高于TNM分期Ⅰ～Ⅱ期患者,Gli1蛋白和VEGF-C在有颈部淋巴结转移患者中的阳性表达率显著高于无颈部淋巴结转移患者,有颈部淋巴结转移患者的MVD与MLVD均显著高于无颈部淋巴结转移患者,差异均有统计学意义(P＜ 0.01或＜ 0.05).甲状腺乳头状癌组织中Gli1蛋白阳性表达与MVD呈正相关(r=0.784,P＜ 0.01),VEGF-C阳性表达与MLVD呈正相关(r=0.529,P＜ 0.01),Gli1蛋白与VEGF-C阳性表达也呈正相关(r=0.586,P＜ 0.01).结论 Gli1蛋白通过Hedgehog信号通路的异常激活得以表达,可能参与了新生微血管的生成；VEGF-C通过介导和启动MAPK信号通路得以表达,可能参与了新生微淋巴管的形成.Gli1蛋白与VEGF-C表达呈正相关,Hedgehog信号通路和MAPK信号通路可能存在相关性.抑制新生微血管和微淋巴管的生成可能成为阻断甲状腺乳头状癌发生颈部淋巴结转移的新靶向.
    목적 연구Gli1단백화혈관내피생장인자(VEGF)-C재갑상선유두상암중적표체급기여갑상선유두상암림상병리특정화경부림파결전이적관계.방법 채용면역조직화학EnVision법측정67례갑상선유두상암환자급32례결절성갑상선종환자병리조직표본중Gli1단백화VEGF-C적표체,동시분별용단극륭항체CD34화D2-40표기각병리표본중적신생미혈관화미림파관,계산종류적미혈관밀도(MVD)화미림파관밀도(MLVD),분석Gli1단백양성표체여MVD적관계、VEGF-C양성표체여MLVD적관계급기여경부림파결전이적관계.결과 갑상선유두상암조직중Gli1단백양성솔、VEGF-C양성솔、MVD、MLVD분별위67.16％ (45/67)、70.15％ (47/67)、23.14±2.06、13.36±1.32,결절성갑상선종조직중분별위43.75％(14/32)、31.25％(10/32)、2.14±0.31、3.53±0.65,량자비교차이유통계학의의(P＜0.05).Gli1단백양성표체여환자적년령、종류대소유상관성(P＜0.05),이VEGF-C양성표체여환자적년령、종류대소무상관성(P＞0.05).Gli1단백화VEGF-C재TNM분기Ⅲ～Ⅳ기갑상선유두상암환자적양성표체솔현저고우TNM분기Ⅰ～Ⅱ기환자,Gli1단백화VEGF-C재유경부림파결전이환자중적양성표체솔현저고우무경부림파결전이환자,유경부림파결전이환자적MVD여MLVD균현저고우무경부림파결전이환자,차이균유통계학의의(P＜ 0.01혹＜ 0.05).갑상선유두상암조직중Gli1단백양성표체여MVD정정상관(r=0.784,P＜ 0.01),VEGF-C양성표체여MLVD정정상관(r=0.529,P＜ 0.01),Gli1단백여VEGF-C양성표체야정정상관(r=0.586,P＜ 0.01).결론 Gli1단백통과Hedgehog신호통로적이상격활득이표체,가능삼여료신생미혈관적생성；VEGF-C통과개도화계동MAPK신호통로득이표체,가능삼여료신생미림파관적형성.Gli1단백여VEGF-C표체정정상관,Hedgehog신호통로화MAPK신호통로가능존재상관성.억제신생미혈관화미림파관적생성가능성위조단갑상선유두상암발생경부림파결전이적신파향.
    Objective To study the expression of Gli1 protein and vascular endothelial growth factor (VEGF)-C in papillary thyroid carcinoma and their relationship with cervical lymph node metastasis.Methods The expression of Gli1 protein and VEGF-C were investigated by immunohistochemical EnVision method in 67 cases of papillary thyroid carcinoma and 32 cases of nodular goiter pathological specimen tissues.Nascent microvascular and micro-lymphatic of all pathological speimen tissues were examined by immunohistochemical monoclonal antibody CD34 and D2-40 staining assay respectively,and the microvascular density (MVD) and micro-lymphatic vessel density (MLVD) were calculated.The relationship between the positive expression of Gli1 protein and MVD,between the positive expression of VEGF-C and MLVD,and their relationship with cervical lymph node metastasis were analyzed.Results The positive rates of Gli1 protein,VEGF-C and MVD,MLVD were significantly higher in papillary thyroid carcinoma than those in nodular goiter [67.16％(45/67) vs.43.75％(14/32),70.15％(47/67) vs.31.25％(10/32),23.14 ± 2.06 vs.2.14 ± 0.31,13.36 ± 1.32 vs.3.53 ± 0.65,P ＜ 0.05].The positive expression of Gli1 protein was related to the patient' s age and the tumor size (P ＜ 0.05),while the positive expression of VEGF-C was not related to the patient' s age and the tumor size (P ＞ 0.05).The positive expression of Gli1 protein and VEGFC were significantly higher in TNM stage Ⅲ-Ⅳ of papillary thyroid carcinoma than those in TNM stage Ⅰ-Ⅱ (P ＜ 0.01) and also was significantly higher with cervical lymph node metastasis than without cervical lymph node metastasis (P ＜ 0.01).MVD and MLVD were significantly higher with cervical lymph node metastasis than without cervical lymph node metastasis (P ＜ 0.05).The positive expression of Gli1 protein was positively correlated with MVD (r =0.784,P＜ 0.01),the positive expression of VEGF-C was positively correlated with MLVD (r =0.529,P ＜ 0.01),the positive expression of Gli 1 protein was positively correlated with the positive expression of VEGF-C (r =0.586,P ＜0.01).Conclusions Gli1 protein which may participate in the formation of nascent microvascular is abnormally activated by the Hedgehog signaling pathway to express,VEGF-C which may be participate in the formation of nascent micro-lymphatic is mediated and started by the MAPK signaling pathways to express.Expressions of Gli1 protein is positively correlated with expressions of VEGF-C,therefore the Hedgehog signaling pathway may be associated with the MAPK signal pathway.Suppressing nascent microvascular and micro-lymphatic may become new target to blockingup papillary thyroid carcinoma cervical lymph node metastasis.
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