Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, San Francisco2Department of Otolaryngology-Head and Neck Surgery, Northwestern University, Chicago, Illinois.
JAMA Otolaryngol Head Neck Surg. 2013 Nov;139(11):1164-70. doi: 10.1001/jamaoto.2013.4501.
Papillary thyroid carcinoma (PTC) is the most common endocrine neoplasm. B-type raf kinase (BRAF) V600E mutation has been proposed as a negative prognostic indicator in PTC, and patients harboring it should receive more aggressive initial therapy.
To assess the significance of BRAF V600E mutation in PTC in the largest US sample to date.
We identified patients from our institution's pathology archives diagnosed as having PTC and meeting criteria for BRAF mutation testing. Medical records were analyzed for BRAF status (positive or negative) and a list of standardized clinicopathologic features.
A total of 429 patients with PTC at an academic medical center.
Clinicopathologic features in patients with PTC with and without BRAF mutation.
Of 429 cases with PTC, 314 (73.2%) were positive for the BRAF mutation and 115 (26.8%) tested negative. BRAF mutation was significantly associated with tumor margin positivity (P = .03) and lymph node metastasis (P = .002) on univariate analysis but not on multivariate study. BRAF mutation was a predictor of male sex (odds ratio [OR], 3.2; 95% CI, 1.4-7.2), total thyroidectomy (OR, 2.6; 95% CI, 1.1-6.2), and a negative predictor of follicular variant PTC (OR, 0.1; 95% CI, 0.1-0.4). There was no significant association between BRAF positivity and tumor multicentricity, lymphovascular invasion, extranodal extension, central neck involvement, advanced stage (stage III or IV), and distant metastasis.
BRAF V600E mutation has been extensively studied in relation to negative prognostic indicators in PTC, with no consistent relationship emerging. Two recent meta-analyses showed an overall association between BRAF status and aggressive disease features and called for tailoring treatment plans in patients accordingly. In this, the largest US study to date, BRAF status was not significantly associated with most clinicopathologic features suggestive of more aggressive disease.
甲状腺乳头状癌（PTC）是最常见的内分泌肿瘤。B 型 Raf 激酶（BRAF）V600E 突变被认为是 PTC 的一个负预后指标，携带该突变的患者应接受更积极的初始治疗。
评估迄今为止美国最大样本中 PTC 中 BRAF V600E 突变的意义。
我们从我们机构的病理档案中确定了符合 BRAF 突变检测标准的被诊断为 PTC 的患者。对病历进行 BRAF 状态（阳性或阴性）和一系列标准化临床病理特征的分析。
共 429 例在学术医疗中心的 PTC 患者。
PTC 患者中 BRAF 突变阳性和阴性患者的临床病理特征。
在 429 例 PTC 病例中，314 例（73.2%）BRAF 突变阳性，115 例（26.8%）检测结果为阴性。BRAF 突变与肿瘤边缘阳性（P=0.03）和淋巴结转移（P=0.002）显著相关，但在多变量研究中则不然。BRAF 突变是男性（比值比[OR]，3.2；95%置信区间[CI]，1.4-7.2）、甲状腺全切除术（OR，2.6；95%CI，1.1-6.2）的预测因素，也是滤泡状变异型 PTC（OR，0.1；95%CI，0.1-0.4）的阴性预测因素。BRAF 阳性与肿瘤多灶性、血管淋巴管侵犯、淋巴结外侵犯、中央颈部受累、晚期（III 或 IV 期）和远处转移之间无显著相关性。
BRAF V600E 突变已在 PTC 的负预后指标方面进行了广泛研究，但没有出现一致的关系。最近的两项荟萃分析显示，BRAF 状态与侵袭性疾病特征之间存在总体关联，并呼吁据此调整患者的治疗计划。在迄今为止最大的美国研究中，BRAF 状态与提示更具侵袭性疾病的大多数临床病理特征之间无显著相关性。
