胰腺上皮内瘤变和胰腺癌组织中TGF-β/Smad信号通路相关蛋白表达  

Expression of TGF-β/Smad signaling transduction associated proteins in pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma

作　　者：郑建明[1] 朱明华[1] 倪灿荣[1] 刘晓红[1] 黄玲[1] 李兆申[2] 

机构地区：[1]第二军医大学附属长海医院病理科,上海200433 [2]第二军医大学附属长海医院消化科,上海200433

出　　处：《临床与实验病理学杂志》2005年第3期327-331,共5页Chinese Journal of Clinical and Experimental Pathology

基　　金：上海市长海医院新一轮学科建设基金(258123)

摘　　要：目的探讨转化生长因子(TGF)β/Smad信号传导通路中Smad相关蛋白、TGFβ1及其Ⅰ、Ⅱ型受体在胰腺上皮内瘤变(PanIN)和胰腺癌组织中表达的意义。方法用免疫组化EnVision法和SP法检测266灶不同级别PanINs和121例胰腺癌组织中Smad相关蛋白、TGFβ1及其Ⅰ、Ⅱ型受体的表达,并联系临床病理学指标进行相关分析。结果高级别PanIN病灶Smad4表达率(60.6%,20/33)低于低级别PanINSmad4表达率(79.8%,186/233)(P<0.05);而高级别PanIN中Smad7,TGFβ1,TGFβRⅡ表达率明显高于低级别PanIN(P<0.05)。胰腺癌组织中,Smad4蛋白表达率在淋巴结转移组和神经受累组低于各自对照组(P<0.05);Smad7、TGFβ1及其Ⅰ、Ⅱ型受体的表达率在淋巴结转移组和神经受累组则分别高于各自对照组(P<0.05)。PanIN和胰腺癌组织中Smad2、4、7蛋白,TGFβ1及其Ⅰ、Ⅱ型受体表达率的差异具有显著性(P<0.01)。结论从低级别PanINs到高级别PanINs再到胰腺癌中,Smad4蛋白表达率逐渐降低,而Smad7、TGFβ1及其Ⅰ、Ⅱ型受体表达率逐渐升高,支持胰腺癌形成的分子模型。Purpose To investigate the significance of Smad proteins,TGF-β1 and TβRⅠand TβRⅡexpression in pancreatic intraepithelial neoplasias (PanINs) and pancreatic adenocarcinoma tissues. Methods The expression of Smads and TGF-β1 and TβRⅠ and TβRⅡ in 266 of focal PanINs and 121 cases of pancreatic adenocarcinomas was determined using the EnVision and S-P methods of immunohistochemistry. The correlation between the expression of Smads and TGF-β1 and TβRⅠ and TβRⅡ and clinicopathological parameters was analyzed. Results The rate of Smad4 expression was significantly lower in high-grade PanIN lesions than low grade PanIN lesions (P<0.05),moreover,the rate of Smad7,TGF-β1 and TβRⅡ expression was significantly higher in high-grade PanIN lesions than low grade PanIN lesions (P<0.05). In pancreatic cancer,the rate of Smad4 expression was significantly lower in lymph node metastasis and perineural invasion compared with non-lymph node metastasis and non-perineural invasion,respectively (P<0.05). The rate of Smad7,TGF-β1 and TβRⅠ and TβRⅡ expression was significantly higher in lymph node metastasis and perineural invasion than those in non-lymph node metastasis and non-perineural invasion,respectively (P<0.05). There was very significant difference in the rates of Smad2,4,7 and TGF-β1 and TβRⅠ and TβRⅡ protein expression between pancreatic cancer and PanIN lesions (P<0.01). Conclusions The rate of Smad4 expression is significantly decreased and the rates of Smad7 and TGF-β1 and TβRⅠ and TβRⅡ expression are significantly increased from low grade PanIN to high-grade PanIN lesions to pancreatic cancer. This supports the molecular model for pancreatic carcinogenesis.

关 键 词：胰腺上皮内瘤变 胰腺癌组织 Smad信号通路 TGF-β1 Smad4 Smad7 Ⅱ型受体 蛋白表达率 信号传导通路 转化生长因子 Vision TGF-βR 相关蛋白 神经受累 病理学指标 Smad2 免疫组化 S-P法 相关分析 分子模型 对照组 转移组 

分 类 号：R735.9[医药卫生—肿瘤] R735.902[医药卫生—临床医学]