甲状腺乳头状癌B-raf基因突变及cyclinD1、p16蛋白表达的相关性及临床病理意义

Mutation of B-raf gene and expression of cyclin D1,p16 proteins in papillary thyroid carcinoma

目的研究甲状腺乳头状癌中B-raf基因突变率及cyclinD1、p16蛋白表达水平,探讨关键信号分子基因突变对相关细胞周期调控因子表达的影响及意义。方法分别应用免疫组化SP法及实时荧光定量PCR法检测100例甲状腺乳头状癌和20例甲状腺良性病变中cyclinD1、p16蛋白的表达及B-raf基因的突变情况。结果甲状腺癌中cyclinD1、p16蛋白表达明显高于良性(P<0.05);其B-raf基因突变率为72%,良性病变组织中未检出突变(P<0.05)。Raf基因突变与患者发病年龄、淋巴结转移及包膜侵犯相关(P<0.05);cyclinD1蛋白阳性与患者年龄、淋巴结转移及B-raf突变相关(P<0.05)。p16蛋白表达仅与患者年龄相关(P<0.05),而与其他指标均无关。甲状腺乳头状癌组织中cyclinD1与p16蛋白的表达具有负相关性(P<0.05)。结论 B-raf基因突变及cyclinD1、p16蛋白高表达均为甲状腺乳头状癌发生的重要分子事件,与肿瘤浸润及转移密切相关,对其进行联合检测有助于甲状腺乳头状癌的预后评估及早期诊断。

Purpose To investigate the expression of cyclinD1,p16 protein and mutation of B-raf gene in papillary thyroid carcinoma and to observe their clinical significance. Methods The expression of cyclinD1,p16 protein in 100 cases of papillary thyroid carcinoma and 20 cases of benign thyroid disease（ nodular goiter） were detected by SP immunohistochemical method and B-raf gene point mutations were analyzed by real-time fluorescence quantitative polymerase chain reaction. Results The positive expression rates of cyclinD1 and p16 protein in papillary thyroid carcinoma were markedly higher than that in normal tissues（ All P〈0. 05）. The mutation rate of B-raf gene was 72%. Braf gene mutations had relationship with age,lymph node metastasis and capsular invasion and metastasis（ P〈0. 05）. The expression of cyclinD1 protein had relationship with age,lymph node metastasis and B-Raf gene mutations（ P〈0. 05）.The expression of p16 protein had relationship with age（ P〈0. 05）,but had no relationship with other index.Conclutions The BRAF（ V600E） mutation,cyclinD1 and p16 protein may play important roles in oncogenesis and progression of papillary thyroid cancer,and their coexpression may be related with the prognosis of patients.