BRAF基因突变与原发性甲状腺功能亢进合并甲状腺乳头状癌的相关性研究

目的:探讨BRAF基因突变与原发性甲状腺机能亢进(甲亢)合并甲状腺乳头状癌（PTC）的关系。方法:选取2011年1月至2016年12月于青岛大学附属医院行手术治疗且病理证实为PTC的甲亢患者。收集患者的性别、年龄、术前血清甲状腺过氧化物酶抗体（TPOAb）、甲状腺球蛋白抗体（TGAb）水平，术前超声特征:结节回声、大小、个数、边界、钙化情况、颈部淋巴结转移与否。记录术后病理特征:癌灶直径（多个癌灶取最大直径）、癌灶个数、是否侵袭被膜、颈部淋巴结转移个数、区域、复发危险度分层及TNM分期。收集患者术后病理蜡块，提取DNA，行普通PCR扩增后，用单纯测序法测得患者BRAF基因的突变率，分析BRAF基因突变与患者临床、超声、病理特征的关系。结果:甲亢合并PTC患者BRAFV600E基因突变率为51.25%（41/80）；各组间比较显示:超声结节边界不清组、病理侵犯被膜组、淋巴结转移组、复发危险度分层中高危组以及TNM Ⅲ-Ⅳ期组BRAFV600E基因突变率均明显升高（均P<0.05）；癌灶直径较大组BRAFV600E基因突变比率明显升高（P=0.002）。结论:甲亢合并PTC患者BRAFV600E基因突变率为51.25%，基因突变与癌灶直径大、被膜侵袭、淋巴结转移、复发危险度及TNM分期高有关。

Correlation between BRAF gene mutation and primary hyperthyroidism combined with papillary thyroid carcinoma

Objective:To investigate the relationship between BRAF gene mutation and primary hyperthyroidism combined with papillary thyroid carcinoma.Methods:Patients with primary hyperthyroidism（hyperthyroidism) confirmed by pathology as thyroid papillary carcinoma（PTC) who underwent surgical treatment in Affiliated Hospital of Qingdao University from January 2011 to December 2016 were selected.Gender，age，preoperative serum TPOAb，TGAb level，preoperative ultrasonic characteristics（nodule echo，size，number，boundary，calcification，cervical lymph node metastasis or not) were collected.Postoperative pathological features were recorded，including tumor diameter（maximum diameter of multiple cancer lesions)，number of cancer lesions，capsule invaded，number of cervical lymph node metastasis，region，risk stratification of recurrence and TNM stage.The postoperative pathological wax blocks of patients were collected.DNA was extracted，and the mutation rate of BRAF gene was measured by simple sequencing method after PCR amplification.The relationship between BRAF gene mutation and clinical，ultrasonic and pathological characteristics of patients was analyzed.Results:The mutation rate of BRAFV600E gene in patients with hyperthyroidism combined with thyroid cancer was 51.25%（41/80)，and the comparison between the groups showed that the mutation rate of BRAF gene was significantly increased in the ultrasound nodule boundary unclear group，pathological invasion capsule group，lymph node metastasis group，high-risk group in the risk stratification of recurrence，and TNM stage Ⅲ，Ⅳ group（all P<0.05).The BRAF gene mutation rate was significantly increased in the group with larger tumor diameter（P=0.002).Conclusion:The mutation rate of BRAFV600E gene in patients with hyperthyroidism combined with nail cancer was 51.25%，which was related to the large diameter of the tumor focus，the invasion of the capsule，lymph node metastasis，the risk of recurrence and the high TNM stage.