原发性胰腺癌中p16基因缺失和突变的研究

Study on Deletion and Mutation of p16 Gene in Primary Pancreatic Carcinoma

目的 探讨p16基因与胰腺癌发生、发展的关系。方法 采用PCR基础缺失分析及PCR -SSCP方法检测p16基因在2 8例胰腺癌的癌组织及相应癌旁组织中的纯合缺失及突变状况 ,并结合临床病理资料进行分析。结果 2 8例原发性胰腺癌组织有 4例出现p16基因纯合缺失 ,5例发生p16基因突变 ,p16基因变异频率为 3 2 1%,2 8例癌旁组织中无一例发现纯合缺失及突变。p16基因变异频率与淋巴结转移 (P <0 0 2 5 )、转移淋巴结个数 (P <0 0 1)及临床分期 (P <0 0 5 )密切相关。结论 p16基因变异在胰腺癌的发生中发挥重要作用 ,是胰腺癌发展过程中的一个晚期分子事件。存在p16基因变异的原发性胰腺癌具有更强的恶性潜能 ,预后更差。

Objective To examine deletion and mutation of p16 gene in primary pancreatic carcinoma to evaluate the relationsip between p16 gene alteration and carcinogenesis of pancreatic carcinoma as well as its progression. Methods Deletion and mutation of p16 gene in 28 primary pancreatic carcinomas and 28 normal tissues adjacent to tumors were detected by PCR-based deletion analysis technique and PCR-SSCP respectively, and the relationship between the results of detection and the clinical parameters was analysed. Results In 28 pancreatic carcinomas, homozygous deletion and mutation of p16 gene were found in 4 and 5 cases respectively. The frequency of p16 gene alteration was 32 1%. p16 gene alteration closely correlated with lymph node metastasis (P<0 025), number of metastatic lymph nodes(P<0 01) and clinical stage (P<0 05). None of p16 gene alteration was found in 28 normal pancreatic tissues adjacent to tumors. Conclusions The alteration of p16 gene may play an important role in carcinogenesis of primary pancreatic carcinoma, which may be a late event in the progression of pancreatic carcinoma. Pancreatic carcinoma with p16 gene alteration has high malignant potential and poor prognosis.