甲状腺微小乳头状癌合并BRAFV600E基因突变伴侧颈淋巴结转移相关危险因素分析

  目的  探讨BRAFV600E基因突变的甲状腺微小乳头状癌侧颈淋巴结转移相关危险因素，对存在基因突变高危因素的微小乳头状癌患者行侧颈淋巴结清扫的适应证进行探索。  方法  回顾性分析2018年1月至2019年8月于四川省肿瘤医院80例行甲状腺全切并行侧颈淋巴结清扫的微小乳头状癌患者的临床资料。术后均行石蜡病理切片BRAFV600E基因测序，根据测序结果分为基因突变组（A组）及基因未突变组（B组），术前年龄、性别等进行统计学分析无显著性差异（P > 0.05），探究术后侧颈淋巴结转移情况。在BRAFV600E已基因突变患者中，按侧颈淋巴结转移与否分为侧颈淋巴结转移组（C组）和侧颈未转移组（D组），分别进行性别、年龄、肿瘤直径、肿瘤位置、甲状腺功能、甲状腺球蛋白、抗甲状腺球蛋白抗体、肿瘤外侵、肿瘤多灶性、中央区淋巴结转移情况与侧颈淋巴结转移的单因素与多因素分析。  结果  80例患者中经BRAFV600E基因测序中50例有突变（A组）以及30例未突变（B组），术前年龄、性别、甲状腺功能、肿瘤位置、多灶性等差异均无统计学意义（P > 0.05），术后A组侧颈淋巴结转移（60%）明显高于B组（27%），差异具有统计学意义（P=0.004）；BRAFV600E基因突变的50例微小乳头状癌患者中，C组年龄≥55岁的12例（24%）出现侧颈淋巴结转移（P=0.038）、中央区淋巴结转移伴侧颈淋巴结转移存在20例（40%）（P=0.011）、肿瘤位置位于中上份的侧颈淋巴结转移19例（38%）（P=0.049）、肿瘤直径≥7.5 mm出现侧颈转移19例（38%）（P=0.021）；而性别、是否存在桥本氏甲状腺炎、甲状腺球蛋白、抗甲状腺球蛋白抗体、肿瘤外侵、多灶性情况同侧颈淋巴结转移差异均无统计学意义（均P > 0.05）。  结论  BRAFV600E基因突变的甲状腺微小乳头状癌患者更易发生侧颈淋巴结转移，且患者年龄 < 55岁、肿瘤直径≥7.5 mm、肿瘤位于中上份、中央区淋巴结转移是存在BRAFV600E基因突变的微小乳头状癌侧颈淋巴结转移的危险因素。 

Risk factors for lateral cervical lymph node metastasis in patients with papillary thyroid carcinoma harboring BRAFV600Emutations

Objective:To investigate the indications of lateral neck lymph node dissection in patients with papillary thyroid carcinoma harboring BRAF^V600Emutations.Methods:From January 2018 to August 2019,80 patients with papillary microcarcinoma who underwent total thyroidectomy and lateral neck lymph node dissection at Sichuan Cancer Hospital&Cancer Institute were retrospectively analyzed.The BRAF^V600Egene was sequenced,and patients were assigned into the gene mutation group(group A)and the no-gene mutation group(Group B)based on sequencing results.There was no significant difference in the preoperative age and sex,so as to explore the cervical lymph node metastasis after surgery;stageⅡ:Fifty patients with BRAF^V600Emutations were assigned into two groups:the lymph node metastasis group(Group C)and the no-metastasis group(Group D).Univariate and multivariate analyses according to sex,age,tumor diameter,tumor location,thyroglobulin levels,anti-thyroglobulin antibody levels,tumor invasion,thyroid function,tumor multifocality,and central lymph node metastasis were performed.Results:Among the 80 patients,50 had BRAF^V600Emutations(group A),while 30 did not(group B).There were no significant differences in preoperative age,sex,thyroid function,tumor location,and multifocality between groups A and B(P>0.05).Postoperative cervical lymph node metastasis was significantly more frequent in group A than in group B(60%vs.27%,P=0.004).Among patients with BRAF^V600Emutations,12(24%)had lateral neck metastasis(P=0.038),20(40%)had central lymph node metastasis with lateral neck lymph node metastasis(P=0.011),19(38%)had lateral neck lymph node metastasis(P=0.049).And 19(38%)had lateral neck metastasis with tumor diameter greater than 7.5mm(38%)(P=0.021);there were no statistically significant differences in gender,presence of Hashimoto's thyroiditis,thyroglobulin,anti-thyroglobulin antibodies,tumor invasion,and multifocal status of ipsilateral cervical lymph node metastasis(P>0.05).Conclusions:Patients with BRAF^V600Emutations were more likely to develop lateral cervical lymph node metastasis.Age<55 years,tumor diameter≥7.5 mm,tumor located in the upper,middle,and central neck regions were risk factors for lateral cervical lymph node metastasis in papillary thyroid carcinoma harboring BRAF^V600Egene mutations.