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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。
Objective To investigate the abnormal expression of p16 gene and the expression of p16 protein in pancreatic cancer and paracancerous tissues and to explore its relationship with the occurrence and development of pancreatic cancer and its clinical significance. Methods The expression of p16 gene and its methylation in 46 cases of pancreatic cancer and its adjacent tissues were detected by immunohistochemistry (SP method) and methylation specific PCR (MSP) respectively. The clinical data were analyzed. Results The positive rate of p16 protein in pancreatic cancer was 41.3% (19/46), while that in paracancerous tissues was 95.7% (44/46). The difference was statistically significant (P <0.01). None of 19 pancreatic cancer samples positive for p16 protein detected methylation. In the 27 cases with deletion of p16 protein, methylation was detected in 18 cases and the methylation rate was 39.1%. Gene methylation was significantly associated with loss of p16 protein (P <0.05). The incidence of p16 gene expression and promoter methylation of p16 gene was not related to the size of pancreatic cancer, gender and age of patients (P> 0.05), but there was statistical significance in the degree of tissue differentiation, lymph node metastasis and PTNM staging (P <0.05). Conclusion The abnormal methylation of p16 gene promoter may affect the expression of p16 protein. The methylation of p16 protein is closely related to the occurrence and development of pancreatic cancer. The p16 methylation and protein expression are candidate markers for the diagnosis and prognosis of pancreatic cancer One of the things.