胰腺癌中p16基因甲基化改变及其蛋白表达分析

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。

p16 gene methylation and its protein expression in pancreatic carcinoma

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 clinical 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 p16 protein.p16 gene methylation was closely related to p16 protein expression in pancreatic carcinoma(P<0.05).The expression of p16,the aberrant methylation in the promoter area of p16 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 p16 gene and p16 protein expression were associated with the development of pancreatic carcinoma and could be used as a putative prognostic indicator for malignancy.