甲状腺增生性疾病中p16^(INK4a)基因甲基化及其表达

Methylation of p16^(INK4a)gene and its expression in thyroid proliferative diseases

目的研究甲状腺增生性疾病中p16^(INK4a)基因的甲基化状况及其与表达之间的关系。方法采用免疫组织化学方法检测45例甲状腺增生性疾病(15例甲状腺乳头状癌,17例甲状腺腺瘤,13例结节性甲状腺肿)样本中p16^(INK4a)蛋白的表达;采用甲基化特异性PCR检测p16^(INK4a)基因的甲基化状况。采用RT-PCR检测其中10例甲状腺增生性疾病(3例甲状腺乳头状癌,5例甲状腺腺瘤,2例结节性甲状腺肿)中p16^(INK4a)mRNA的表达。结果 45例甲状腺增生性疾病样本中,8例检测到p16^(INK4a)基因异常甲基化,19例p16^(INK4a)蛋白表达阳性;p16^(INK4A)基因异常甲基化与其蛋白表达之间呈负相关(r=-0.293 4,P=0.038 7)。10例甲状腺增生性疾病样本中,5例检测到转录产物;p16^(INK4A)基因异常甲基化与其转录水平之间呈负相关(r=-0.654 7,P=0.04)。结论 p16^(INK4a)基因甲基化与p16^(INK4a)基因失活有关,但并不与失活完全一致;p16^(INK4a)基因甲基化可能在甲状腺增生性疾病中起作用。

Objective To investigate the methylation status of pl6^（INK4a） gene and its expression in throid proliferative diseases. Methods The expression of pl6^（INK4a） protein in 45 cases of throid proliferative diseases （15 cases of papillary thyroid carcinoma, 17 cases of throid adenoma, 13 cases of nodular goiter） was detected by immunohistochemistry. Methylation status of pl6^（INK4a） gene was detected by methylation specific PCR. The expression of pl6^（INK4a） mRNA in 10 cases of thyroid proliferative diseases （3 cases of papillary thyroid carcinoma, 5 cases of throid adenoma, 2 cases of nodular goiter） was detected by RT-PCR. Results In 45 cases of thyroid proliferative diseases, aberrant methylation of pl6 gene was detected in 8 cases, and positive expression of pl6^（INK4a） protein was found in 19 cases. The aberrant methylation of p16 ^（INK4a） gene was negatively related to its expression of protein（r = -0. 293 4, P =0.038 7） . Among the 10 cases of thyroid proliferative diseases, gene transcripts was detected in 5 cases, and the aberrant methylation of pl6^（INK4a） gene was negatively related to its transcription （ r = - 0.654 7, P = 0.04）. Conclusion The methylation of pl6^（INK4a） may lead to the loss of its expression, but they are not always concordant. The methylation of pl6^（INK4a） may play a role in the pathogenesis of thyroid proliferative diseases.