甲状腺癌组织端粒酶激活与p16基因失活的研究

The Association between Activation of Telomerase and Inactivation of the p16 Gene in Thyroid Cancer

目的:探讨甲状腺癌细胞增殖、分化与端粒酶激活及抑癌基因p16失活(缺失突变)之间可能存在的联系。方法:应用TRAP、多重PCR、免疫组化法检测42例甲状腺癌与16例癌旁组织端粒酶活性、p16基因外显子2缺失、p16蛋白表达。结果:甲状腺癌组端粒酶活性90.48%,高于癌旁组织(P<0.01);甲状腺癌p16基因外显子2纯合缺失率28.57%,相应癌旁组未检出(P<0.01);甲状腺癌p16蛋白表达缺失率40.48%,高于癌旁组(P<0.05);甲状腺癌p16蛋白表达缺失率高于p16基因外显子2缺失率。结论:端粒酶激活与p16基因失活以及p16蛋白表达下调可能是甲状腺癌变过程中的重要分子事件,甲状腺癌中p16基因失活可能是端粒酶激活的一种途径。

Objective： To study the relationship between telomerase activity and inactivation （deletion mutation） of the p16 gene in thyroid cancer. Methods： Telomerase activation was detected with TRAP, p16 gene deletion with multiplex PCR and p16 protein expression with an immunochemical technique in 42 cases of thyroid cancer and 16 normal tissues. Results：Telomerase activity was significantly increased in cancer tissues （90.48%） compared to normal tissues （P〈0.01）. The deletion rate of p16 exon 2 was 28.57% in thyroid cancer, and this deletion was not detected in any tumor-adjacent tissues （P〈0.01）. P16 protein expression was decreased in thyroid cancer compared to normal tissue （P〈0.05）. Ablation of p16 protein expression occurred 40.48% more often than deletion of p16 exon 2. Conclusion： The activation of telomerase, deletion of the p16 gene, and ablation of p16 protein expression might occur early in thyroid cancer and play a critical role in tumor development. In human thyroid cancer loss of the p16 gene may activate telomerase.