超声引导下细针穿刺洗脱液测定BRAF^(V600E)突变丰度预测甲状腺乳头状癌颈部淋巴结转移

BRAF^(V600E)mutation abundance determined based on ultrasound-guided fine needle aspiration samples for predicting lymph node metastasis in papillary thyroid cancer

目的探索超声引导下细针穿刺洗脱液测定BRAF^(V600E)突变丰度在预测甲状腺乳头状癌(PTC)颈部淋巴结转移中的临床价值。方法收集在上海交通大学医学院附属瑞金医院2020年1月至12月间行甲状腺手术且病理证实为PTC的1046例患者,术前均行超声引导下细针穿刺活检测定BRAF^(V600E)突变丰度。根据淋巴结转移情况将患者分为淋巴结转移组(419例)和无淋巴结转移组(627例)。采用χ2检验或t检验分析2组患者间的临床特征(性别、年龄、肿瘤最大径、结节数目、结节位置)以及突变丰度之间是否存在差异,并采用二元Logistic回归进行多因素分析,同时构建受试者操作特征(ROC)曲线评估BRAF^(V600E)基因突变丰度预测PTC患者淋巴结转移的诊断效能。结果淋巴结转移组中男性、<45岁、肿瘤最大径≥1 cm、多发结节数目以及多侧结节比例高于无淋巴结转移组(32.0%vs 19.9%;72.1%vs 54.5%;38.9%vs 19.0%;25.8%vs 18.0%;16.2%vs 10.4%),差异均具有统计学意义(χ2=19.56、32.62、50.63、9.06、7.78;P<0.001、<0.001、<0.001、=0.003、=0.005);PTC伴有淋巴结转移的BRAF^(V600E)突变丰度高于无淋巴结转移者[(32.44±20.23)%vs(27.21±20.82)%],差异具有统计学意义(t=-4.29,P<0.001)。多因素回归分析结果提示男性、年龄、最大径≥1 cm、多发结节、BRAF^(V600E)突变丰度高为PTC颈部淋巴结转移的独立危险因素(OR=1.935、0.425、2.578、1.651、2.057;P均<0.05)。ROC曲线显示BRAF^(V600E)突变丰度预测颈部淋巴结转移的敏感度、特异度、阳性预测值、阴性预测值和曲线下面积分别为48.69%、65.71%、48.69%、65.71%、0.574。结论BRAF^(V600E)突变丰度高的PTC患者更容易发生淋巴结转移,BRAF^(V600E)突变丰度高是PTC颈部淋巴结转移的危险因素。

Objective To assess the clinical value of the abundance of BRAF^(V600E)mutation detected in ultrasound-guided fine needle aspiration samples in predicting cervical lymph node metastasis(LNM)of papillary thyroid carcinoma(PTC).Methods A total of 1046 patients with pathologically confirmed PTC between January 2020 and December 2020 at Ruijin Hospital,Shanghai Jiao Tong University School of Medicine were collected.Ultrasound-guided fine-needle aspiration samples were collected to determine the abundance of BRAF^(V600E)mutation before surgery.Patients were classified into lymph node metastasis group(n=419)and no lymph node metastasis group(n=627)based on lymph node metastasis.The correlation between clinical characteristics(sex,age,tumor diameter,number of nodes,nodal location,and mutation abundance)and cervical LNM in PTC patients was analyzed usingχ2 test or t-test.Multifactorial analysis was performed by binary logistic regression analysis,and the diagnostic efficacy of BRAF^(V600E)mutation abundance in predicting cervical LNM in PTC patients was assessed by constructing receiver operating characteristic(ROC)curves.Results The proportions of males,patients<45 years old,patients with tumor maximum diameter≥1 cm,patients with multiple nodes,and those with multiple bilateral nodes in patients with cervical LNM was significantly higher than those in patients without(32.0%vs 19.9%,72.1%vs 54.5%,38.9%vs 19.0%,25.8%vs 18.0%,and 16.2%vs 10.4%;χ2=19.56,32.62,50.63,9.06,and 7.78;P<0.001,<0.001,<0.001,=0.003,and=0.005,respectively);the abundance of BRAF^(V600E)mutation was significantly higher in PTC patients with cervical LNM than in those without[(32.44±20.23)%vs(27.21±20.82)%,t=-4.29,P<0.001].Multifactorial regression analysis suggested that male gender,age,maximum diameter≥1 cm,multiple nodes,and high abundance of BRAF^(V600E)mutation were independent risk factors for cervical LNM in PTC(OR=1.935,0.425,2.578,1.651,and 2.057,respectively;P<0.05).The sensitivity,specificity,positive predictive value,negative predictive value,and area under the curve of BRAF^(V600E)mutation abundance in predicting cervical LNM were 48.69%,65.71%,48.69%,65.71%,and 0.574,respectively.Conclusion The detection of BRAF^(V600E)mutation abundance can provide a reference for clinical decision making in cervical LNM resection in patients with PTC.