Endocrine Surgery, Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
J Clin Endocrinol Metab. 2013 Sep;98(9):3702-12. doi: 10.1210/jc.2013-1584. Epub 2013 Aug 22.
Existing evidence is controversial regarding the association between BRAF mutation status and aggressive features of papillary thyroid cancer (PTC). Specifically, no study has incorporated multiple surgical practices performing routine central lymph node dissection (CLND) and thus has patients who are truly evaluable for the presence or absence of central lymph node metastases (CLNMs).
Consecutive patients who underwent total thyroidectomy and routine CLND at 4 tertiary endocrine surgery centers were retrospectively reviewed. Descriptive and bivariable analyses examined demographic, patient, and tumor-related factors. Multivariable analyses examined the odds of CLNM associated with positive BRAF status.
In patients with classical variant PTC, bivariate analysis found no significant associations between BRAF mutation and aggressive clinicopathologic features; multivariate analysis demonstrated that BRAF status was not an independent predictor of CLNM. When all patients with PTC were analyzed, including those with aggressive or follicular subtypes, bivariate analysis showed BRAF mutation to be associated with LNM, advanced American Joint Committee on Cancer (AJCC) stage, and histologic subtype. Multivariable analyses showed BRAF, age, size, and extrathyroidal extension to be associated with CLNM.
Although BRAF mutation was found to be an independent predictor of central LNM in the overall cohort of patients with PTC, this relationship lost significance when only classical variant PTC was included in the analysis. The usefulness of BRAF in predicting the presence of LNM remains questionable. Prospective studies are needed before BRAF mutation can be considered a reliable factor to guide the treatment of patients with PTC, specifically whether to perform prophylactic CLND.
BRAF 突变状态与甲状腺乳头癌（PTC）侵袭性特征之间的关联存在争议。具体来说，尚无研究纳入常规中央淋巴结清扫术（CLND）的多种手术实践，因此无法评估中央淋巴结转移（CLNM）的存在与否。
回顾性分析了在 4 个三级内分泌外科中心行全甲状腺切除术和常规 CLND 的连续患者。描述性和双变量分析检查了人口统计学、患者和肿瘤相关因素。多变量分析检查了与 BRAF 阳性相关的 CLNM 可能性。
在经典变异型 PTC 患者中，双变量分析发现 BRAF 突变与侵袭性临床病理特征之间无显著关联；多变量分析表明 BRAF 状态不是 CLNM 的独立预测因子。当分析所有 PTC 患者，包括侵袭性或滤泡亚型患者时，双变量分析显示 BRAF 突变与淋巴结转移、晚期美国癌症联合委员会（AJCC）分期和组织学亚型相关。多变量分析显示 BRAF、年龄、大小和甲状腺外延伸与 CLNM 相关。
尽管 BRAF 突变被发现是 PTC 患者总体队列中中央 LNM 的独立预测因子，但当仅包括经典变异型 PTC 进行分析时，这种关系失去了意义。BRAF 在预测 LNM 存在方面的作用仍存在疑问。在 BRAF 突变可以被认为是指导 PTC 患者治疗的可靠因素之前，需要进行前瞻性研究，特别是是否进行预防性 CLND。
