TGF-β1、Smad4蛋白和TβRⅡ在胆囊癌发生与发展中的作用

The role of TGFβ1,Smad4,and TβRⅡ in the initiation and progression for gallbladder carcinoma

目的：通过检测原发性胆囊癌细胞中TGF-β1、Smad4蛋白和TβRⅡ在不同时期的表达,探讨它们之间的相互关系及其在胆囊癌发生发展中的作用。方法：应用免疫组化SP法检测30例胆囊癌、11例胆囊腺瘤及30例胆囊炎中TGF-β1、Smad4蛋白和TβRⅡ的表达情况,并分析它们与胆囊癌临床病理之间的关系。结果：30例胆囊癌中TGF-β1、Smad4蛋白和TβRⅡ的阳性率分别为73.3%、20.0%和16.7%,胆囊腺瘤中阳性率分别为90.9%、63.7%、54.5%,在胆囊炎中阳性率分别为96.7%、93.3%、90.0%。TGF-β1在胆囊癌中表达低于胆囊炎（P〈0.05）;Smad4蛋白、TβRⅡ在胆囊癌中表达均低于胆囊炎和胆囊腺瘤（P〈0.05）。Ⅰ-Ⅱ期胆囊癌TGF-β1阳性率低于Ⅲ-Ⅴ期（P〈0.05）,而Smad4蛋白、TβRⅡ阳性率明显高于Ⅲ-Ⅴ期（P〈0.05）。TGF-β1在有转移的胆囊癌组织中表达率为94.1%,明显高于无转移者（P〈0.05）。结论：TGF-β1的表达降低可能与胆囊细胞的恶性转化和生长失控有关;TGF-β1高表达不能抑制肿瘤细胞增殖,可能与Smad4及TβRⅡ的低表达有关,且TGF-β1高表达与胆囊癌的发展及浸润、转移有关。

Objective：To investigate the relationship between the expressions of the transforming growth factor beta 1 （TGF- β1 ） , Smad4, and TβR Ⅱ in the different stages of gallbladder carcinoma and discuss their roles in the development of gallbladder carcinoma. Methods：Immunohistochemical SP method was used to examine the expression of TGF-β1, Smad4, and TβR Ⅱ in 30 cases of gallbladder carcinoma, 11 cases of gallbladder adenoma, and 30 cases of cholecystitis. The relationship between the expressions of TGF- β1, Smad4 and TβR Ⅱ and the clinicopathological features of gallbladder carcinoma were analyzed. Results：The positive rates of TGF- β1, Smad4 and TβR Ⅱ was 73.3% , 20% , and 16. 7% in 30 cases of gallbladder carcinoma; 90.9% , 63.7% , and 54.5% in 11 cases of gallbladder adenoma; 96.7% , 93.3% , and 90% in 30 cases of cholecystitis. The expression of TGF-β1 was significantly lower in gallbladder carcinoma than that in cholecystitis （ P 〈 0.05 ）. The expressions of Smad4 and TβR Ⅱ were significantly lower in gallbladder carcinoma than that in cholecystitis （P 〈0.05 ）. Gallbladder carcinoma at stages Ⅰ and Ⅱ had lower TGF-131 expression but higher Srnad4 and T13R Ⅱ expression than those at stage m and V （ P 〈 0.05）. TGF-β1 expression was significantly higher （94.1% ） in gallbladder carcinoma with metastasis than that without metastasis （P 〈 0.05 ）. Conclusion ：The decreased expression of TGF-β1 in gallbladder carcinoma may be related with the cell malignant transformation and uncontrolled growth. Over-expression of TGF-β could not inhibit the proliferation of gallbladder carcinoma which may be due to the decreased expression of Smad4 and TβR Ⅱ. The high expression of TGF-β1 is related with the progression, invasion, and metastasis of gallbladder carcinoma.