基因检测在甲状腺结节诊断中分层应用模式的研究  

Stratified application of gene expression in diagnosis of thyroid nodules

作　　者：管文燕[1] 郑金榆[1] 聂岭[1] 吴鸿雁[1] Guan Wenyan;Zheng Jinyu;Nie Ling;Wu Hongyan(Department of Pathology,the Affiliated Drum Tower Hospital of Nanjing University Medical School,Nanjing 210008,China)

机构地区：[1]南京大学医学院附属鼓楼医院病理科,南京210008

出　　处：《中华病理学杂志》2024年第3期264-268,共5页Chinese Journal of Pathology

基　　金：国家自然科学基金面上项目(82372988);南京市卫生科技发展专项一般性课题(YKK21077)。

摘　　要：目的探讨单基因BRAF V600E检测与多基因检测作为甲状腺结节诊断分子标志物的价值及分层应用的模式。方法收集南京大学医学院附属鼓楼医院2020年12月至2022年7月1117例甲状腺结节切除术患者,均行术前穿刺样本基因检测和细胞病理检查。以术后组织病理结果为“金标准”,比较单基因BRAF V600E检测和多基因检测的诊断性能,并结合甲状腺细胞病理学Bethesda报告系统(BSRTC)分类,分析基因检测在甲状腺结节诊断中的应用模式。结果1117例甲状腺结节切除术患者,男性285例,女性832例,中位年龄46岁(24~76岁)。经术后组织病理学证实为甲状腺癌1040例,良性结节77例。多基因检测的灵敏度、诊断符合率显著高于单基因检测(87.0%∶80.8%,P<0.01)、(87.9%∶82.1%,P<0.01)。多基因检测以检出BRAF V600E突变为主,其次是CCDC6-RET(E1-E12)融合突变、ETV6-NTRK3融合突变、KRAS突变。对于BSRTCⅠ~Ⅴ类结节,多基因检测相较于单基因检测具有更高的灵敏度(81.9%∶72.8%,P<0.01)、野生型恶性风险较低(47.6%∶57.7%,P=0.069)。其中,BSRTCⅠ类结节,两者灵敏度其差异无统计学意义(P>0.05);BSRTCⅢ类结节,多基因检测灵敏度更高,差异有统计学意义(86.3%∶74.0%,P<0.01)。结论基因检测可作为甲状腺结节良恶性诊断的有效辅助工具,且多基因的诊断性能更优。本文提出一种优化的基因检测分层应用模式:初次细针穿刺活检,推荐同时进行基因检测;对于初次细针穿刺活检选择单基因但未检测突变的BSRTCⅢ类结节,重复细针穿刺活检推荐进行多基因检测。Objective To investigate the value of BRAF V600E and multigene detection and stratified application for the diagnosis of thyroid nodules.Methods A total of 1117 patients with thyroid nodules resection at Nanjing Gulou Hospital from December 2020 to July 2022 were enrolled in the study.Fine needle aspiration(FNA)and core biopsy samplings were performed for cytopathologic examination and genetic testings;the findings were combined with BSRTC classification.The diagnostic performance of BRAF V600E and multigene detection were compared.Results Among the 1,117 patients who underwent thyroid nodules resection,285 were male and 832 were female,with a median age of 46 years(range:24-76 years).Postoperative histopathologic examination confirmed 1040 cases of thyroid cancer and 77 cases of benign nodules.The sensitivity(87.0%vs.80.8%,P<0.01)and diagnostic accuracy(87.9%vs.82.1%,P<0.01)of multigene detection were significantly higher than those of BRAF V600E detection.The result of multigene detection showed that BRAF V600E mutation was the most common finding,followed by CCDC6-RET(E1-E12)fusion,ETV6-NTRK3 fusion,and KRAS mutation.Multigene detection had a higher sensitivity(81.9%vs.72.8%,P<0.01)and lower cancer risk in wild-type(47.6%vs.57.7%,P=0.069)than BRAF V600E detection in BSRTCⅠ-Ⅴlesions.Compared with BRAF V600E detection,multigene had no significant difference of sensitivity in BSRTCⅠlesions,but significantly higher sensitivity(86.3%vs 74.0%,P<0.01)in BSRTCⅢlesions.Conclusions Genetic detection can be used as an effective tool for the diagnosis of thyroid nodules.A stratified application of molecular markers in the diagnosis of thyroid nodules is proposed.Combined with FNA,single gene or multigene detection both can effectively assist in the diagnosis of thyroid nodules.Moreover,multigene detection is superior to single gene detection.For BSRTCⅢlesion with wild-type BRAF,multigene detection can be considered with a repeated FNA.

关 键 词：基因 甲状腺结节 分子诊断技术 

分 类 号：R581[医药卫生—内分泌]