甲状腺乳头状癌中BRAF基因突变与中央区淋巴结转移的关系及临床意义

目的：阐明BRAF基因突变在甲状腺乳头状癌中央区淋巴结转移中的作用。方法：采集整理2012年至2014年间于北京大学肿瘤医院头颈外科行手术治疗的275例甲状腺乳头状癌患者，对其肿瘤组织进行BRAF基因检测并通过单因素、多因素Logistic回归模型探索中央区（Ⅵ区）淋巴结转移的危险因素。结果：275例患者中，女性224例（81.5%），男性51例（18.5%）。有57.8%（159/275）的患者发生中央区淋巴结转移，BRAF的突变率为53.8%（148/275），其中，超声下有无钙化（ORadjusted=1.47，95%CI：1.10~1.98，P=0.01)、肿瘤的长径（ORadjusted=1.48，95%CI：1.04~2.30，P=0.048）及患者的年龄（ORadjusted=1.48，95%CI：1.04~2.30，P=0.048）与淋巴结转移显著相关。分层分析后，BRAF突变在超声下边界尚清组（ORadjusted=3.19，95%CI：1.18~9.43，P=0.023）和超声下无钙化组（ORadjusted=4.84，95%CI：1.68~13.84，P=0.003）均与淋巴结转移正相关。结论:甲状腺乳头状癌患者具有一定比例的中央区淋巴结转移率，BRAF突变是甲状腺乳头状癌的特征性分子事件，钙化、低年龄组及肿瘤长径较长的患者更易发生中央区淋巴结转移。尽管超声下边界尚清或无钙化，但一旦合并BRAF突变则更易发生淋巴结转移，中央区淋巴结清扫术是有效的治疗方法。

Relationship and clinical significance between mutated BRAF with prophylactic cen-tral-neck nodal dissection in papillary thyroid carcinoma

Objective:To evaluate the molecular diagnosis marker of papillary thyroid carcinoma (PTC),the relationship between lymphatic metastasis of central neck compartment PTC,and the opera-tion indication of prophylactic central neck dissection.Methods:We conducted a retrospective study, including 275 PTC patients and detected their BRAF mutation rates during 201 2 and 201 4 and explored the risk factors of the central node lymphatic metastasis by Logistic regression model.Results:Of the 275 PTC patients,224 (81 .5%)were female and 51 (1 8.5%)were male.BRAF mutational rates were 53.8% (1 48 /275)and lymphatic metastasis 57.8% (1 59 /275).Multivariate analysis showed calcifica-tion (ORadjusted =1 .47,95%CI:1 .1 0 -1 .98,P =0.01 ),tumor diameter (ORadjusted =1 .48,95%CI:1 .04 -2.30,P =0.048)and age (ORadjusted =1 .48,95%CI:1 .04 -2.30,P =0.048)were associa-ted with lymphatic metastasis.In stratified analysis,BRAF mutation (ORadjusted =3.1 9,95%CI:1 .1 8 -9.43,P =0.023 )in clear boarder group and BRAF mutation (ORadjusted =4.84,95% CI:1 .68 -1 3.84,P =0.003)in calcification group were more likely to have lymphatic metastases.Conclusion:Central neck metastasis takes up a high ratio in papillary thyroid cancer patients,BRAF mutation in pa-pillary thyroid carcinoma is a characteristic molecular event.Furthermore,patients with calcification un-der ultrasound detection,lower age group and longer tumor diameter are more susceptible to suffer central neck metastasis.Especially for stratified analysis,non-calcified BRAF mutation or BRAF mutation with clear border under ultrasound detection are more susceptible to suffer central neck metastasis,and radical prophylactic central neck dissection should be carried on for these patients.