口腔鳞状细胞癌中上皮-间充质转化标志物E-钙黏蛋白、波形蛋白、β-联蛋白及转化生长因子β1的表达

The expression of E-cadherin, vimentin, β-catenin, transforming growth factor-β1 in oral squamous cell carcinomas

目的 分析在口腔鳞状细胞癌（oral squamous cell carcinomas,OSCC）中E-钙黏蛋白、波形蛋白、β-联蛋白及转化生长因子β1 （transforming growth factor-β1,TGF-β1）的表达情况,探讨其表达强度与OSCC病理的关系.方法 收集2007年1月至2013年11月暨南大学第一附属医院病理科及广东省口腔医院＆#183;南方医科大学附属口腔医院病理科89例OSCC（OSCC组）及20例正常口腔黏膜标本（正常组）,将OSCC组标本分为Ⅰ级（25例）、Ⅱ级（34例）、Ⅲ级（30例）,运用免疫组织化学EnVisionTM两步法对OSCC组及正常组标本行抗原-抗体反应,应用半定量十三点评分法（染色强度评分＆#215;阳性细胞比率评分）评价免疫组化结果,统计分析各项指标与OSCC分化程度之间的关系,以及各项指标间的相关性.结果 E-钙黏蛋白在正常组中评分中位数为9.00,OSCC组Ⅰ、Ⅱ、Ⅲ级中的评分分别为9.00、6.00和6.00,正常组与OSCC组比较差异有统计学意义（Z=-4.211,P=0.000）,评分与分化程度有关（P=0.000）;波形蛋白在正常组中评分为0.00,在OSCC组Ⅰ、Ⅱ、Ⅲ级中评分分别为0.00、0.00和4.00,正常组与OSCC组差异有统计学意义（Z=-3.675,P=0.000）,评分与分化程度有关（P=0.000）;β-联蛋白在正常组中评分为9.00,在OSCC组Ⅰ、Ⅱ、Ⅲ级中评分分别为3.00、4.00和3.00,正常组与OSCC组差异有统计学意义（Z=-6.300,P=0.000）,评分与分化程度有关（P=0.017）;TGF-β1在正常组中评分为2.00,在OSCC组Ⅰ、Ⅱ、Ⅲ级中评分分别为3.00、4.00和6.00,正常组与OSCC组差异有统计学意义（Z=-3.329,P=0.000）,评分与分化程度有关（P=0.000）;E-钙黏蛋白与β-联蛋白之间存在显著正相关（r=0.327,P=0.002）,与波形蛋白间存在显著负相关（r=-0.386,P=0.001）,与TGF-β1之间存在显著负相关（r=-0.304,P=0.004）;波形蛋白与TGF-β1之间存在显著正相关（r=0.401,P=0.000）.结论 E-钙黏蛋白和β-联蛋白在癌细胞中表达下调,波形蛋白表达上调,TGF-β1有下调趋势,提示在口腔肿瘤发生和发展中出现了上皮-间充质转化现象,β-联蛋白和TGF-β1可能通过调控上皮-间充质转化现象影响肿瘤的发生和发展.

Objective To investigate the expression of E-cadherin,vimentin,β-catenin and transforming growth factor-β 1（TGF-β 1） in oral squamous cell carcinomas（OSCC）.Methods Eighty-nine cases of OSCC and 20 cases of normal oral mucosa were collected.Then the 89 cases of OSCC were classified as grade Ⅰ,Ⅱ,Ⅲ.The semiquantitative method was used to calculated the positive intensity and positive rate.The reiationship between the OSCC differentiation and the four biomarkers was analyzed.Results The median of E-cadherin was 9.00 in the normal tissue,9.00,6.00 and 6.00 in OSCC Ⅰ,Ⅱ and Ⅲ,respectively.There was significant difference between the normal group and OSCC group（Z=-4.211,P=0.000）.The median of vimentin was 0.00 in the normal tissue,0.00,0.00 and 4.00 in OSCC Ⅰ,Ⅱ and Ⅲ,respectively.There was significant difference between the normal group and OSCC group（Z=-3.675,P=0.000）.The median of β-catenin was 9.00 in the normal tissue,3.00,4.00 and 3.00 in OSCC Ⅰ,Ⅱ and Ⅲ,respectively.There was significant difference between the normal group and OSCC group（Z=-6.300,P=0.000）.The median of TGF-β1 was 2.00 in the normal tissue,3.00,4.00 and 6.00 in OSCC Ⅰ,Ⅱ and Ⅲ,respectively.There was significant difference between the normal group and OSCC group（Z=-3.329,P=0.000）.E-cadherin expression was positively correlated to β-catenin expression（r=0.327,P=-O.002）,negtively correlated to vimentin expression（r=-0.386,P=0.001） and positively correlated to TGF-β1 expression（r=-0.304,P=0.004）.Vimentin expression was positively correlated to TGF-β 1 expression （r=0.401,P=0.000）.Conclusions E-cadherin and β-catenin in OSCC had a down-regulated expression,while the vimentin has an up-regulated expression.