Lupi Cristiana, Giannini Riccardo, Ugolini Clara, Proietti Agnese, Berti Piero, Minuto Michele, Materazzi Gabriele, Elisei Rossella, Santoro Massimo, Miccoli Paolo, Basolo Fulvio
Departments of Surgery and Endocrinology, University of Pisa, 56126 Pisa, Italy.
J Clin Endocrinol Metab. 2007 Nov;92(11):4085-90. doi: 10.1210/jc.2007-1179. Epub 2007 Sep 4.
Because very few studies have examined the correlation between BRAF mutations and clinicopathological features of papillary thyroid carcinoma (PTC), we analyzed here a large and homogeneous cohort of patients with PTC for the presence of the BRAF mutation.
We examined BRAF mutations in a consecutive series of 500 PTC patients who underwent surgery in the Department of Surgery of the University of Pisa, and we correlated the presence of the mutation with clinicopathological parameters of the patients: age, gender, tumor size, presence of tumor capsule, extrathyroidal invasion, multicentricity, presence of node metastases, and tumor class.
BRAF (exon 15) mutation was examined by PCR-single strand conformational polymorphism followed by DNA sequencing in laser-capture microdissected tissue samples.
In this study, BRAF mutation was found in 219 of 500 cases (43.8%). In particular, we found the most common BRAF V600E mutation in 214 cases (42.8%), BRAF K601E mutation in three cases (0.6%), BRAF VK600-1E (0.2%) in one case, whereas in one case we found a new 14-bp deletion with concomitant 2-bp insertion, VKSR600-3del and T599I, respectively. BRAF V600E was associated with extrathyroidal invasion (P < 0.0001), multicentricity (P = 0.0026), presence of nodal metastases (P = 0.0009), class III vs. classes I and II (P < 0.00000006), and absence of tumor capsule (P < 0.0001), in particular in follicular- and micro-PTC variants. By multivariate analysis, the absence of tumor capsule remained the only parameter associated (P = 0.0005) with BRAF V600E mutation.
Our data suggest that BRAF V600E mutation is associated with high-risk PTC and in particular in follicular variant with invasive tumor growth.
由于极少有研究探讨BRAF突变与甲状腺乳头状癌（PTC）临床病理特征之间的相关性，我们在此分析了一大组同质化的PTC患者队列，以检测BRAF突变的存在情况。
我们检测了在比萨大学外科接受手术的连续500例PTC患者中的BRAF突变，并将突变的存在情况与患者的临床病理参数相关联：年龄、性别、肿瘤大小、肿瘤包膜的存在情况、甲状腺外侵犯、多中心性、淋巴结转移的存在情况以及肿瘤分级。
通过聚合酶链反应-单链构象多态性检测BRAF（第15外显子）突变，随后对激光捕获显微切割的组织样本进行DNA测序。
在本研究中，500例病例中有219例（43.8%）检测到BRAF突变。具体而言，我们在214例（42.8%）中发现了最常见的BRAF V600E突变，3例（0.6%）发现BRAF K601E突变，1例（0.2%）发现BRAF VK600-1E，而在1例中我们发现了一个新的14碱基缺失并伴有2碱基插入，分别为VKSR600-3del和T599I。BRAF V600E与甲状腺外侵犯（P < 0.0001）、多中心性（P = 0.0026）、淋巴结转移的存在情况（P = 0.0009）、III级与I级和II级（P < 0.00000006）以及无肿瘤包膜（P < 0.0001）相关，尤其是在滤泡状和微小PTC变体中。通过多变量分析，无肿瘤包膜仍然是与BRAF V600E突变相关的唯一参数（P = 0.0005）。
我们的数据表明，BRAF V600E突变与高危PTC相关，尤其是在具有侵袭性肿瘤生长的滤泡状变体中。
