胰腺癌中p16基因甲基化改变及其蛋白表达分析  

p16 gene methylation and its protein expression in pancreatic carcinoma

作　　者：杨卫华[1] 王春友[1] 朱求实[1] 阎雷[1] 许州[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院胰腺外科中心,湖北武汉430022

出　　处：《中国普通外科杂志》2007年第5期446-450,共5页China Journal of General Surgery

摘　　要：目的探讨胰腺癌与癌旁组织中p16基因启动子区异常甲基化的改变及其蛋白表达的特点,以及其与胰腺癌发生发展的关系。方法分别采用免疫组化SP法及甲基化特异PCR(MSP)检测46例人胰腺癌和癌旁组织中p16基因表达及其甲基化的水平,并结合临床资料进行分析。结果胰腺癌中p16蛋白表达率为41.3%(19/46),而癌旁组织表达率为95.7%(44/46),两者有差异显著性(P<0.01)。p16蛋白阳性的19例胰腺癌标本中均未检出基因甲基化;p16蛋白缺失的27例标本中有18例检出基因甲基化,甲基化率为39.1%。p16基因甲基化与蛋白缺失有明显关系(P<0.05)。p16基因表达及其启动子区甲基化的发生率与胰腺癌的大小,患者性别?年龄的差异无显著意义(P>0.05),但与组织分化程度?淋巴结转移?PTNM分期有显著意义(P<0.05)。结论p16基因启动子的异常甲基化可影响p16蛋白的表达,它们与胰腺癌的发生发展有关;p16甲基化和蛋白表达可能成为胰腺癌诊断及预后的候选标志物之一。Objective To investigate aberrant methylation in the promoter area of p16 gene and p16 protein expression in human pancreatic carcinoma and in the corresponding tumor-adjacent tissues, and evaluate their role in the carcinogenesis and progression of tumor and its dinical significance. Methods Immunohistochemistry and MSP （methylation-specific PCR ） were performed on 46 samples of pancreatic carcinoma and their corresponding tumor-adjacent tissue specimens for p16 and its methylation. Results Expression rate of p16 protein was 41.3 % （19/46） in pancreatic carcinomas, 95.7 % （44/46） in corresponding tumor-adiucent tissues. Through MSP, the methylation rate in pancreatic carcinomas was 39. 1%. No gene methylation was found in 19 cases expressing p 1 6 protein, p 16 gene methylation was closely related to p 16 protein expression in pancreatic carcinoma （ P 〈 0.05 ）. The expression of p16, the aberrant methylation in the promoter area of p 16 gene were no relationship with clinicopathological characteristics, such as tumor size, patient＇s sex and age （P 〉 0. 05 ）; but were significantly related to the PTNM staging, histological differentiation, distant metastasis and lymph node metastasis （ P 〈 0.05 ）. Conclusions Methylation in the promoter of p 16 gene and p 16 protein expression were associated with the development of pancreatic carcinoma and could be used as a putative prognostic indicator for malignancy.

关 键 词：胰腺肿瘤 P16基因 甲基化 甲基化特异性PCR P16蛋白表达 

分 类 号：R735.9[医药卫生—肿瘤]