摘要
背景与目的:甲状腺微小乳头状癌(papillary thyroid microcarcinoma,PTMC)发病率迅速上升,对其治疗一直存在争议。PTMC风险评估的关键指标大多系手术后临床病理参数,以回顾性总结为主,对临床治疗的指导价值有限。该研究旨在分析BRAF^(V600E)及端粒酶逆转录酶(telomerase reverse transcriptase,TERT)启动子突变与PTMC危险因素的相关性及在PTMC的风险评估中的价值。方法:收集甘肃省肿瘤医院头颈外科2014年10月—2016年6月首诊治疗的107例PTMC患者,采用聚合酶链反应(polymerase chain reaction,PCR)直接测序法检测BRAF^(V600E)及TERT启动子突变,应用χ~2检验和二元logistic回归分析对数据进行统计学分析。结果:107例PTMC患者中,BRAF^(V600E)和TERT启动子突变率分别为68.2%和11.2%。单因素分析显示,有无被膜侵犯及淋巴结转移与BRAF^(V600E)突变均有显著相关性(P均<0.01)。年龄、性别、被膜侵犯、不良病理亚型及淋巴结转移与TERT启动子突变及BRAF^(V600E)和TERT同时突变均有显著相关性(P均<0.05)。多因素分析显示,与BRAF^(V600E)突变显著相关的因素包括:甲状腺被膜侵犯(P=0.012)及淋巴结转移(P=0.000)。与TERT启动子突变显著相关的因素包括:男性(P=0.004)、年龄<45岁(P=0.026)、甲状腺被膜侵犯(P=0.004)、不良病理亚型(P=0.030)及淋巴结转移(P=0.043)。与BRAF^(V600E)和TERT同时突变显著相关的因素包括:男性(P=0.022)、甲状腺被膜侵犯(P=0.023)、不良病理亚型(P=0.041)及淋巴结转移(P=0.030)。结论:BRAF^(V600E)及TERT启动子突变可能成为甲状腺微小乳头状癌的分子诊断标志和预后指标,同时出现BRAF^(V600E)及TERT启动子突变可能与患者的不良预后相关,对PTMC风险评估有重要价值。
Background and purpose:The incidence of papillary thyroid microcarcinoma(PTMC)has been increasing rapidly,and its treatment is controversial.Most of the key indicators of PTMC risk assessment are clinical and pathological parameters after operation,which are mainly based on retrospective review limiting guiding value for clinical treatment.The objective of this study was to analyze the correlation between the mutations of BRAF-(V600E )and telomerase reverse transcriptase(TERT)promoter and PTMC risk factors,and their value in the risk assessment of PTMC.Methods:This study retrospectively analyzed 107 cases of PTMC which were diagnosed after the surgery at the Department of Head and Neck Surgery in Gansu Province Tumor Hospital from October 2014 to June 2016.The mutations of BRAF^V600E and TERT promoter were detected by polymerase chain reaction(PCR)direct sequencing.We analyzed the data usingχ-2 test and binary logistic regression analysis.Results:Among 107 patients with PTMC,BRAF^V600E and TERT promoter mutation rates were 68.2%and 11.2%,respectively.Single factor analysis showed that the presence of membrane invasion and lymph node metastasis was significantly correlated with BRAF^V600E mutation(P〈0.01).Age,gender,capsular invasion,poor pathologic subtype and lymph node metastasis were significantly correlated with TERT promoter mutation and BRAF^V600E and TERT mutation at the same time(P〈0.05).Multifactorial analysis showed that the factors closely related to the BRAF^V600E mutation included capsular invasion(P=0.012)and lymph node metastasis(P=0.000).The following factors were closely associated with TERT promoter mutation:male(P=0.004),age〈45 years(P=0.026),capsular invasion(P=0.004),pathological subtype(P=0.030)and lymph node metastasis(P=0.043).The following factors were closely related to the simultaneous mutations of BRAF^V600E and TERT:male(P=0.022),capsular invasion(P=0.023),poor pathological subtype(P=0.041)and lymph node
作者
薛金才
刘勤江
田尤新
侯小峰
XUE Jincai;LIU Qinjiang;TIAN Youxin;HOU Xiaofeng(Department of Head and Neck Surgery,Gansu Province Tumor Hospital,Lanzhou 730050,Gansu Province,China)
出处
《中国癌症杂志》
CAS
CSCD
北大核心
2018年第5期335-341,共7页
China Oncology
基金
兰州市科技计划项目(2017-4-75)