原发性胰腺癌中p16基因突变及其蛋白表达的研究

目的：探讨p16基因与胰腺癌发生的关系。方法：采用PCR基础缺失分析，PCR－SSCP及免疫组织化学方法检测28例胰腺癌组织，相应癌旁组织和4例正常胰腺组织中p16基因缺失，突变及其蛋白表达状况，并结合临床病理资料进行分析，结果：28例原发性胰腺癌组织中4例发生p16基因纯合缺失。5例发生p16基因突变，p16基因变异频率为32．1％，28例癌旁组织和4例正常胰腺组织中未发现纯合缺失及突变。p16基因变异频率与淋巴结转移（P＜0．025），转移淋巴结个数（P＜0．01）及临床分期（P＜0．05）密切相关。28例原发性胰腺癌的癌组织，癌旁组织和4例正常胰腺组织p16蛋白阳性表达率分别为57．1％（16／28），85．7％（24．28）和100％（4／4），癌组织中p16蛋白阳性表达率与组织学分化（P＜0．05），淋巴结转移（P＜0．05），转移淋巴结个数（P＜0．05）及临床病理分期（P＜0．05）密切相关。结论：p16基因变异及其蛋白失表达可能是胰腺癌发生发展过程中重要因素之一，而且二者均可作为评估胰腺癌恶性程度及其侵袭能力的有用指标，存在p16基因变异及蛋白失表达的原发性胰腺癌具有更强的恶性潜能。

The study on deletion, mutation of p16 gene in primary pancreatic carcinoma

Objective To examine homozygous deletion, mutation of p16 gene and expression p16 protein in primary pancreatic carcinmoa, and explore the relationship between p16 gene alteration and carcinogenesis of pancreatic carcinoma as well as its progression.Methods The deletion, mutation of p16 gene and the expression of p16 protein in 28 cases of primary pancreatic carcinoma and 28 paracancerous and 4 normal pancreatic tissues were detected by the technique of PCR based deletion, PCR SSCP and immunohisochemistry respectively, and the relation between the results of detection and the clinical parameters were analysised.Results Of all the 28 cases of pancreatic carcinoma, homozygous deletion and mutation of p16 gene were found in 4 and 5 cases respectively:the frequency of p16 gene alteration was 32.1%, which was closely correlated to lymph node metastasis( P <0.025),the number of metastatic lymph nodes( P <0.01),clinical stage( P <0.05).None of alteration of p16 gene were found in 28 paracancerous and 4 normal pancreatic tissues. The p16 protein positive rate was 57.1%(16/28) in pancreatic carcinoma, 85.7%(24/28) in paracancerous tissues and 100%(4/4) in normal pancreatic tissues respectively. In pancreatic carcinoma, the p16 positive rate was closely correlated with histologic grade( P <0.05),myphnodemelastasis( P <0 05),the number of metastastic lymph node( P <0 05)and clinical stage( P <0.05).Conclusion The alteration of p16 gene and the absence of p16 protein play one of important roles in carcinogenesis of primary pancreatic carcinoma and in the progression of pancreatic carcinoma. Pancreatic carcinoma with p16 gene alteration or absence of p16 protein has strong malignant potential and poor prognosis.