BRAF^(V600E)突变和cN0期甲状腺乳头状癌淋巴结转移相关性研究

Study on the correlation between BRAF^(V600E) mutation and lymphatic metastases in papillary thyroid cancer staged preoperatively as N0

目的:研究BRAF^(V600E)基因突变在cN0期甲状腺乳头状癌(PTC)中的突变发生率,探讨BRAF^(V600E)突变与PTC(cN0期;肿瘤直径≤2cm)颈部淋巴结转移的相关性。方法:应用巢式PCR基因测序法检测72例行预防性中央区淋巴结清扫的PTC石蜡包埋组织中BRAF^(V600E)突变情况,结合患者临床病理资料,分析引起BRAF^(V600E)基因突变和PTC(cN0期)中央区淋巴结转移的相关性。结果:BRAF^(V600E)基因突变率为47.22%(34/72),中央区颈部淋巴结隐性转移率为36.11%(26/72)。cN0期PTC淋巴结转移的危险因素单因素分析发现:与肿瘤大小(P=0.016)、双侧肿瘤(P=0.010)、多灶性肿瘤(P=0.006)、包膜浸润(P=0.024)、BRAF基因突变(P=0.008)相关。淋巴结转移相关因素变量纳入Logistic多因素回归分析发现:与肿瘤大小(OR=2.674,95%CI=1.702~3.997)、肿瘤多灶性(OR=1.371,95%CI=1.065~2.087)、包膜浸润(OR=0.540,95%CI=0.396~0.794)、BRAF突变(OR=1.647,95%CI=1.101~2.463)具有相关性,为cN0期PTC淋巴结转移的危险因素。结论:临床检查、B超术前检查及术中探查无淋巴结转移的N0期PTC患者隐性淋巴结转移发生率为36.11%,BRAF基因突变、肿瘤大小、多灶性、包膜侵犯可能是预测中央区颈部淋巴结转移的危险因素,有中央区淋巴结转移危险因素者应选择性预防性中央区淋巴结清扫。

Objective：To study the prevalence of BRAF-（V600E）mutations in small（≤2cm）papillary thyroid carcinoma（PTC）,explore the correlation with occult central nodal metastasis（CNM）of clinically-nodal negative（cN0）neck for small（≤2cm）papillary thyroid carcinoma（PTC）.Method：Primary tumor tissue（paraffin-embedded）from 72 patients with small（≤2cm）cN0PTC who underwent prophylactic central neck dissection（pCND）was tested for BRAF mutation.by nested PCR,the factors of lymph node metastasis such as clinicopathologic including tumor size,multifocality,extrathyroidal invasion,and BRAF mutations were analyzed.Prediction scores were generated using logistic regression models and BRAF was evaluated to see if it was a risk factor for CNM.Result：The prevalence of BRAF was 47.22%（34/72）while the rate of CNM was 36.11%（26/72）.Univariate analysis showed that the risk factors of lymph node metastasis for cN0 PTC were significantly correlated with tumor size（P=0.016）,bilateral tumor（P=0.010）,multifocality（P=0.026）,extrathyroidal invasion（P=0.024）,and BRAF mutations（P=0.041）.Univariate analysis showed that tumor size（OR=2.674,95%CI=1.702-3.997）,multifocality（OR=1.371,95% CI=1.065-2.087）,extrathyroidal invasion（OR=0.540,95%CI=0.396-0.794）and BRAF（OR=1.647,95%CI=1.101-2.463）were risk predictors of CNM.Conclusion：The incidence of central neck micrometastatic disease is 36.11%in patients with PTC deemed N0 preoperatively by clinical examination and ultrasound of the neck lymph nodes and intraoperatively by inspection of the central compartment.The factors of high risk of CNM included tumor size,multifocality,extrathyroidal invasion,BRAF mutations.When a patient has the risk factors of lymph node metastasis should be electived prophylactic CCND.