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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。
Objective To investigate the expression of pathogenesis of TGF-β1 pathway in alveolar rhabdomysarcoma (ARMS) and embryonal rhabdomysarcoma (ERMS) and its clinicopathological significance. Methods Immunohistochemical EnVision and one-step RT-PCR were used to detect the expression of TGF-β1 mRNA and protein in TGF-β / Smads signal transduction pathway in 9 cases of ARMS and 16 cases of ERMS. Results The 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% and 66.7% in ERMS, 75%, 83.3% and 75% respectively. There was no significant difference between the two groups. The positive rate of TGF-β1 mRNA in ARMS was 55.6% (5/9) and the positive rate in ERMS was 62.5% (10/16). Pathological grading and clinical staging showed that there was a negative correlation between TGF-βRⅠ and pathological grade (P <0.05), and positive correlation between Smad2 / 3 and pathological grade in ARMS group (P <0.05). There was a positive correlation between Samd7 and pathological grade (P <0.01). TGF-β1 and TGF-βRⅡ showed a highly positive correlation with pathological grade and clinical stage in both groups (P <0.01). Conclusion The expression of TGF-β / Smad signaling pathway in both acinar and embryonal rhabdomyosarcoma is closely related to the pathological grade and clinical stage of rhabdomyosarcoma, suggesting that TGF-β / Smads signaling pathway may be involved in the pathogenesis of rhabdomyosarcoma Mechanism, can be used as a reference index of the prognosis of rhabdomyosarcoma.