Department of Otolaryngology-Head, Neck Surgery, Chungnam National University, School of Medicine, 640 Daesa-Dong, Chung-Gu, Daejeon 301-721, South Korea.
J Clin Endocrinol Metab. 2012 Nov;97(11):3996-4003. doi: 10.1210/jc.2012-2444. Epub 2012 Aug 28.
Few reports have determined whether preoperative detection of the BRAF V600E mutation in fine-needle aspiration biopsy (FNAB) may influence determination of surgical extent such as prophylactic central lymph node dissection (CLND) in patients with papillary thyroid carcinoma (PTC).
Our objectives were to investigate whether preoperative BRAF analysis may assist determination of surgical extent, including prophylactic CLND with variable clinicopathological risk factors for central lymph node metastasis, in patients with PTC and clinically node-negative neck.
From July 2009 to May 2011, we prospectively enrolled 148 PTC patients with clinically node-negative neck who received a total thyroidectomy and prophylactic CLND. BRAF mutation by pyrosequencing was tested on preoperative FNAB specimens. The relationships between occult central lymph node metastasis and preoperative BRAF mutation or clinicopathological factors were analyzed. Additionally, we assessed the associations between preoperative BRAF mutation status and various clinicopathological characteristics of PTC revealed postoperatively.
The prevalence of the BRAF V600E mutation was 53.4%, and the rate of occult central lymph node metastasis was 25.7%. Multivariate analysis showed that tumor size over 1 cm [P = 0.006; odds ratio (OR) = 3.559], perithyroidal invasion (P = 0.023; OR = 2.893), and preoperative positive BRAF mutation (P = 0.029; OR = 2.727) were independent risk factors for the presence of occult central lymph node metastasis. BRAF mutation examined in FNAB specimens, compared with the wild-type allele, strongly predicted perithyroidal invasion (48 vs. 29%; P = 0.017), extracapsular spread (65 vs. 45%; P = 0.017), occult central lymph node metastasis (35 vs. 15%; P = 0.004), and advanced TNM stage (44 vs. 28%; P = 0.035). In the multivariate analysis, patients with preoperative positive BRAF mutation were significantly more likely (P = 0.023; OR = 2.848) to have occult central lymph node metastasis.
Preoperative BRAF analysis by FNAB and primary tumor size based on ultrasonography may assist in predicting occult central lymph node metastasis in patients with PTC and clinically node-negative neck.
鲜有报道明确术前细针穿刺抽吸活检(FNAB)中 BRAF V600E 突变的检出是否会影响甲状腺乳头状癌(PTC)患者预防性中央淋巴结清扫术(CLND)的手术范围,如预防性 CLND。
我们的目的是探讨术前 BRAF 分析是否有助于确定手术范围,包括对伴有中央淋巴结转移不同临床病理危险因素的 PTC 患者行预防性 CLND,此类患者临床颈部淋巴结阴性。
2009 年 7 月至 2011 年 5 月,我们前瞻性纳入 148 例临床颈部淋巴结阴性的 PTC 患者,这些患者均接受甲状腺全切除术和预防性 CLND。应用焦磷酸测序法对术前 FNAB 标本进行 BRAF 突变检测。分析隐匿性中央淋巴结转移与术前 BRAF 突变或临床病理因素之间的关系。此外,我们评估了术前 BRAF 突变状态与术后发现的各种 PTC 临床病理特征之间的关联。
BRAF V600E 突变的发生率为 53.4%,隐匿性中央淋巴结转移率为 25.7%。多因素分析显示,肿瘤直径>1cm(P=0.006;优势比[OR],3.559)、甲状腺周围侵犯(P=0.023;OR,2.893)和术前 BRAF 阳性突变(P=0.029;OR,2.727)是隐匿性中央淋巴结转移的独立危险因素。FNAB 标本中 BRAF 突变与野生型等位基因相比,强烈预测甲状腺周围侵犯(48%比 29%;P=0.017)、包膜外扩散(65%比 45%;P=0.017)、隐匿性中央淋巴结转移(35%比 15%;P=0.004)和更晚期的 TNM 分期(44%比 28%;P=0.035)。多因素分析显示,术前 BRAF 阳性突变的患者发生隐匿性中央淋巴结转移的可能性显著更高(P=0.023;OR,2.848)。
基于超声的术前 FNAB 和原发肿瘤大小的 BRAF 分析可能有助于预测临床颈部淋巴结阴性的 PTC 患者隐匿性中央淋巴结转移。