甲状腺结节BRAF V600E突变检测的临床意义  

Clinical role of BRAF V600E mutation testing in thyroid nodules

作　　者：万汉锋[1] 张彬[1] 王勇[1] 肖汀[1] 郭会芹[1] 刘文胜[1] 鄢丹桂[1] 徐震纲[1] 唐平章[1] 

机构地区：[1]北京协和医学院中国医学科学院肿瘤医院肿瘤研究所头颈外科,100021

出　　处：《中华耳鼻咽喉头颈外科杂志》2014年第6期468-472,共5页Chinese Journal of Otorhinolaryngology Head and Neck Surgery

基　　金：协和青年基金资助和中央高校基本科研业务费专项资金（3332013030）

摘　　要：目的 分析甲状腺结节检测BRAF V600E突变的临床意义.方法 收集2013年39月80例患者（83个）甲状腺结节细针穿刺（fine-needle aspiration,FNA）样本,采用PCR扩增BRAF第15外显子并进行测序,将BRAF V600E突变结果、细胞学诊断与术后病理诊断进行比较,同时分析BRAF V600E突变在甲状腺乳头状癌中的检出率及其与患者性别、年龄、肿瘤大小、淋巴结转移、多发病灶、AJCC分期等临床病理特征之间的相关性.结果 83个甲状腺结节选择观察33个,48个接受手术治疗,2个未接受手术建议.48个手术病例中共有25个BRAF V600E突变阳性结节,其中13个FNA诊断恶性,其余12个FNA诊断无法确定性质,该25个突变阳性结节术后病理均为甲状腺乳头状癌.在23个BRAF V600E突变阴性结节中FNA诊断恶性5个,良性2个,无法确定性质16个,术后病理15个甲状腺乳头状癌,1个甲状腺髓样癌,7个甲状腺良性病变.FNA结合BRAF V600E突变检测将FNA诊断甲状腺结节敏感度由43.9％提高到73.2％,x2检验比较提示二者差异有统计学意义（P＜0.05）.40例甲状腺乳头状癌BRAF V600E突变率为62.5％,在20例侵犯甲状腺被膜外的肿瘤中BRAF V600E突变16例（80.0％）,在20例没有侵犯被膜外的肿瘤中BRAF V600E突变9例（45.0％）,单因素分析提示BRAF V600E突变与甲状腺被膜外侵犯相关（x2=5.227,P=0.022）,而与性别、年龄、肿瘤大小、淋巴结转移、多发病灶、AJCC分期等临床病理特征之间无相关性.结论 甲状腺结节FNA细胞学检测BRAF V600E突变能提高甲状腺结节良恶性诊断准确性,同时可能有助于术前筛选出高危甲状腺癌病例.Objective To evaluate the clinical role of BRAF V600E mutation testing in fine-needle aspirates （FNA） of thyroid nodules.Methods This study included 83 nodules in 80 patients who underwent FNA from March 2013 to September 2013.Cytological specimens were collected and BRAF exon 15 was examined by polymerase chain reaction （PCR）.DNA sequencing and analysis were performed.Diagnostic performances of cytology and cytology with BRAF V600E mutation analysis were compared according to postoperative pathological diagnosis.The ralation of BRAF V600E mutation with clinical factors including sex and age of patients,tumor size,lymph node metastasis,multifocality,and AJCC stage were analyzed.Results Of 83 nodules,33 nodules were clinically observed,and 48 nodules underwent surgery,and suggestions of surgery were refused in 2 nodules.Among 48 nodules with surgery,BRAF V600E mutation was found in 25 nodules with histologic confirmation of papillary thyroid carcinoma after thyroidectomy,13 of the 25 nodules were cytologically diagnosed as carcinoma and 12 were indeterminate.Among the 23 BRAF V600E negative noudles,5 were cytologically diagnosed as carcinoma,2 were benign,and 16 were indeterminate; 15 nodules were histologic confirmation of papillary thyroid carcinoma after thyroidectomy,1 nodule was medullary thyroid carcinoma,and 7 nodules were benign.Biomolecular analysis significantly increased cytology sensitivity for papillary thyroid carcinoma from 43.9％ to 73.2％ （P ＜ 0.05）.Direct DNA sequencing showed that the presence of BRAF V600E mutation was 62.5％ in 40 thyroid papillary nodules.There were 16 BRAF-positive nodules （80.0％） among 20 papillary thyroid nodules with extrathyroidal extension,however there were 9 BRAF-negative nodules （45.0％） among 20 papillary thyroid nodules without extrathyroidal extension.Univariate analysis indicated the BRAF V600E mutation was associated with extrathyroidal extension （x2 =5.227,P =0.022）,but not with sex,age,tumor size,lymph node metastasis,multifocal

关 键 词：甲状腺结节 活组织检查 细针 原癌基因蛋白质B-raf 突变 

分 类 号：R446.8[医药卫生—诊断学]