甲状腺肿瘤细胞中p16基因的表达和突变

Expression and Alterations ofp 16 Gene in Human Primary Thyroid Neoplasm

目的:研究抑癌基因p16在甲状腺肿瘤中的表达及突变。方法:采用免疫组织化学法检测60例甲状腺肿瘤细胞中p16蛋白的表达;采用聚合酶链式反应检测甲状腺肿瘤细胞中p16基因的缺失及外显子_15′CpG岛异常甲基化。结果:60例甲状腺肿瘤中p16蛋白阳性表达为46.7%(28/60);30例腺瘤中p16蛋白阳性表达分别为60.0%(18/30);30例腺癌中则为33.3%(10/30)。60例甲状腺肿瘤中p16基因缺失为13.3%(8/60),30例腺癌中p16基因缺失为26.7%(8/30);30例腺瘤中无缺失(0/30),组间比较差异有显著性(P<0.05)。60例甲状腺肿瘤中p16基因外显子_15′CpG岛异常甲基化为15.0%(9/60);30例腺癌中为30.0%(9/30);30例腺瘤中无外显子_15′CpG岛异常甲基化(0/30),组间比较差异有显著性(P<0.001)。结论:抑癌基因p16参与了甲状腺肿瘤的发生发展,p16基因的缺失和外显子_15′CpG岛异常甲基化在甲状腺恶性肿瘤中起一定的作用,并可能是甲状腺肿瘤中p16基因失活的主要机制。

Objective： To investigate the relationship between expression and alteration of p 16 gene in human primary thyroid neoplasm. Method： 60 cases of thyroid neoplasma were examined for the expression of p 16 proteins by immunohistochemical method, including 30 cases of adenomas and 30 cases of carcinomas, and the alterations and hypermethylations of p 16 gene were examined by polymerase chain reaction （PCR） and PCR-base methylation assay. Results： Expression of p 16 proteins were detected in 28 cases of thyroid neoplasm （28/60, 46.7% ）, including 18 cases of thyroid adenomas （TA） and 10 cases of thyroid carcinomas （TC）, Expression of p 16 and p63 proteins were detected in 6 cases （6/15, 40.0% ） and 5 cases （ 5/15, 33.3% ） of thyroid follicular adenomas （FTA） respectively, Deletion of p 16 gene were detected in 8 cases （8/60, 26.7% ） of TC, and no deletion was found in TA. There was hypermethylation at the 5＇CpG island of exon 1 of p 16 gene in 9 cases （9/30, 30.0% ） of TC, no hypermethylation was found in 30 cases of TA. Conclusions： p 16 may play important role in occurrence and development of TC. 5＇CpG island of exon 1 of p 16 gene hypermethylation may be an important mechanism related to p 16 gene inactivation in human primary thyroid neoplasm.