胰腺癌中p16基因甲基化改变及其蛋白表达分析

目的研究p16基因启动子区异常甲基化改变和p16蛋白表达在胰腺癌与癌旁组织中的表达特点,探讨其与胰腺癌发生发展与临床的关系。方法分别以免疫组化法(SP法)及甲基化特异PCR(MSP)检测46例胰腺癌及其癌旁组织中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),两者相比差异有统计学意义(P<0.01)。p16蛋白阳性的19例胰腺癌标本,均未检出基因甲基化;p16蛋白缺失的27例标本,有18例检出基因甲基化,甲基化率为39.1%。基因甲基化与p16蛋白缺失明显相关(P<0.05),p16基因表达及p16基因启动子区甲基化的发生率与胰腺癌的大小、患者性别、年龄的差异无统计学意义(P>0.05),但在组织分化程度、有无淋巴结转移、PTNM分期上有统计学意义(P<0.05)。结论p16基因启动子异常甲基化改变可能影响p16蛋白的表达;p16甲基化、蛋白表达与胰腺癌的发生发展密切相关,p16甲基化和蛋白表达是胰腺癌患者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 its protein expression in human pancreatic carcinoma and the corresponding adjacent tissues,and evaluate their role in the carcinogenesis and progression of tumor and the clinical significance.Methods Immunohistochemistry and methylation-specific PCR (MSP) were performed on 46 samples of pancreatic carcinoma and their corresponding adjacent tissues for detection of p16 and its methylation.Results The expression rate of p16 protein was detected in 19 of 46 (41.3%) pancreatic carcinomas,while in 44 of 46 (95.7%) corresponding paracancerous tissues.MSP revealed that 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).There was no relationship among the expression of p16,the aberrant methylation in the promoter area of p16 gene,clinicopathological characteristics such as tumor size,patient's sex and age (P>0.05).They were significantly related to the PTNM staging,histological differentiation,distant metastasis and lymph node metastasis (P<0.05).Conclusion Methylation in the promoter of p16 gene and its protein was associated with the development of pancreatic carcinoma and could be used as a putative prognostic indicator for malignancy.