人乳头瘤病毒16型E7蛋白和TGF-β1/Smads信号传导通路在宫颈病变中的表达及其意义

Investigation of the expression of human papillomavirus type 16 E7,transforming growth factor β1/Smads signal transduction system in different stages of human cervical lesions.

目的:检测宫颈病变组织中人乳头瘤病毒16型(HPV-16)E7蛋白以及转化生长因子β1(TGF-β1)介导的细胞信号传导通路中TGF-β1及其Ⅱ型受体(TβRⅡ)和Smad4蛋白的表达,探讨人乳头瘤病毒感染和TGF-β1/Smads信号传导通路在肿瘤形成及演进过程中可能的作用机制。方法:免疫组织化学SP法检测141例石蜡包埋的不同病变宫颈组织中E7,TGF-β1,TβRⅡ和Smad4的表达,通过计算机图片摄像分析系统统计其在各种病变中表达水平的差异。结果:病变由良性到恶性的发展过程中,TGF-β1和Smad4的表达水平逐渐增高(P<0·001,P<0·05);肿瘤分化程度降低,TGF-β1的表达水平增高(P<0·001)。TβRⅡ表达在不同阶段和组织学类型的宫颈病变中无显著差异(P>0·05)。E7蛋白阳性者TGF-β1的表达水平较阴性者高(P<0·05),而TβRⅡ和Smad4的表达则无显著差异(P>0·05)。结论:TGF-β1在宫颈病变中的表达与病变良恶性和肿瘤分化程度有关,TGF-β1高表达是宫颈恶性肿瘤的表现之一;HPV-16感染可能影响到TGF-β1/Smads信号传导通路的功能。

Objective:To detect the expression of human papillomavirus type 16 E7 protein and TGFβ1,TβRⅡ and Smad4 protein in human cervical neoplasms and to explore their possible roles in tumor formation and progression.Methods:141 paraffin embedded samples of different cervical lesions were examined using immunohistochemical staining technique,being immunostained with antibodies against E7,TGF-β1,TβRⅡ and Smad4 respectively.The differences of their expression were detected by computer with picture analyzing software.Results:E7,TGF-β1,TβRⅡand Smad4 were expressed in cytoplasm.With the progressing from benign to malignant lesions,the expression of TGF-β1 and Smad4 were getting significantly stronger progressively (P<0.001 and P<0.05),wihle TβRⅡ was not.The higher expression level of TGF-β1 was observed in poorly differentiated tumor (P<0.001).The samples that were E7 positive got a higher production of TGF-β1 than those of E7 negative.Conclusion:The expression of TGF-β1 has certain relationship with the development of cervical neoplasms and the tumor differentiation.A higher level of TGF-β1 indicats the malignance of cervical lesions.HPV-16 infection may has effects on the function of TGF-β1/Smads system.