胚胎性和腺泡型横纹肌肉瘤中TGF-β1及其受体、Smad2/3和Smad7的表达

Expression of TGF-β1,TGF-βRⅠ,TGF-βRⅡ,Smad2/3 and Smad7 in alveolar and embryonal rhabdomyosarcoma

目的探讨转化生长因子β1(TGF-β1)通路相关基因在腺泡型横纹肌肉瘤(alveolar rhabdomysarcoma,ARMS)和胚胎性横纹肌肉瘤(embryonal rhabdomysarcoma,ERMS)中的表达及发病机制和临床病理意义。方法采用免疫组化EnVision和一步法RT-PCR方法,检测9例ARMS和16例ERMS中TGF-β/Smads信号通路中相关蛋白表达和TGF-β1mRNA的表达水平。结果 TGF-β1、TGF-βRⅠ、TGF-βRⅡ、Smad2/3和Smad7蛋白表达率在ARMS分别为66.7%、88.9%、77.8%、77.8%、100%,在ERMS中为66.7%、66.7%、75%、83.3%、75%,两者差异无统计学意义;TGF-β1mRNA在ARMS阳性率为55.6%(5/9),在ERMS阳性率为62.5%(10/16)。病理分级和临床分期分析结果显示:ARMS组中TGF-βRⅠ与病理分级呈负相关(P<0.05),Smad2/3与病理分级呈正相关(P<0.05),ERMS组中Samd7与病理分级呈正相关(P<0.01)。TGF-β1、TGF-βRⅡ在两组病例中显示与病理分级和临床分期呈高度正相关(P<0.01)。结论腺泡状和胚胎性横纹肌肉瘤中均存在TGF-β/Smad信号通路相关成分的表达,与横纹肌肉瘤的病理分级和临床分期有密切关系,提示TGF-β/Smads信号通路可能参与横纹肌肉瘤发病机制,可作为横纹肌肉瘤预后的一个参考指标。

Purpose To investigate the expression pathogenesis and clinical pathology of transforming growth factor β1 （TGF-β1） pathway genes in the alveolar and embryonal rhabdomyosarcoma （ARMS/ERMS）.Methods Immunohistochemical EnVision method was used to examine the expression of TGF-β1,TGF-βRⅠ,TGF-βRⅡ,Smad2/3,Smad7 and RT-PCR to detect TGF-β1 mRNA in 25 specimens of rhabdomyosarcoma.Results The positive expression rates of TGF-β1,TGF-βRⅠ,TGF-βRⅡ,Smad2/3 and Smad7 were 66.7%,88.9 %,77.8%,77.8 % and 100% in ARMS,and 66.7%,66.7 %,75%,83.3% and 75% in ERMS,respectively.The mRNA expression of TGF-β1 in ARMS and ERMS was 55.6%（5/9）and 62.5%（10/16）.The results of the pathological grades and clinical stage showed：in ARMS,TGF-βRⅠ was significantly negative correlation with the pathological grades （P0.05）,Smad2/3 were significantly positive correlation with the pathological grades （P0.05）;In ERMS,Samd7 were most significantly positive correlation with the pathological grades （P0.01）.TGF-β1 and TGF-βRⅡ were with the pathological grades and clinical stage （P0.01）.Conclusions The expression of TGF-β1,TGF-βRⅠ,TGF-βRⅡ,Smad2/3 and Smad7 plays certain important roles in the development of ARMS and ERMS and has significant correlation with the pathological grades and clinical stage.TGF-β/Smads signal pathway related components are important markers for the evaluation of malignant degree and prognosis in rhabdomysarcoma.