Semsar-Kazerooni Koorosh, Morand Grégoire B, Payne Alexandra E, da Silva Sabrina D, Forest Véronique-Isabelle, Hier Michael P, Pusztaszeri Marc P, Tamilia Michael, Payne Richard J
Faculty of Medicine, McGill University, Montréal, QC, Canada.
Department of Otolaryngology-Head and Neck Surgery, Jewish General Hospital, McGill University, 3755 Côte-Sainte-Catherine Road, Montréal, QC, H3T 1E2, Canada.
J Otolaryngol Head Neck Surg. 2022 Mar 4;51(1):9. doi: 10.1186/s40463-022-00559-9.
In clinical practice, thyroid tumor size plays a critical role in the staging of thyroid malignancies and in the selection of nodules that should undergo ultrasound-guided fine-needle aspiration. Thyroid tumor size is influenced by the elapsed time since the beginning of oncogenesis and by the presence of somatic mutations driving growth, such as BRAF mutations, associated with aggressive phenotypes, and RAS-like mutations, associated with more indolent behavior. Although large nodules are often considered to be more alarming, the true impact of tumor size on prognosis remains controversial. The aim of this study was to assess the relationship between mutational status, tumor size and aggressiveness, with emphasis on BRAF and RAS-like mutations.
We conducted a multicentric retrospective chart review in Montréal, Canada, of all patients who underwent thyroid surgery between January 2016 and December 2020, with well-differentiated thyroid cancer on final pathology, and who had undergone molecular testing revealing the presence of BRAF mutations or RAS-like mutations (NRAS, HRAS or KRAS).
We included 214 cases. There were 117 (54.7%) cases of BRAF and 97 (45.3%) cases of RAS-like mutations. The BRAF group was statistically associated with a smaller mean tumor size when compared with the RAS group of 1.55 cm and 2.04 cm, respectively. In a multivariate model, tumors with BRAF mutations were also more likely to display aggressive pathological features, including extra-thyroidal extension, lymph node metastasis, columnar cell features, tall cell histology, or hobnail histology (OR 26.69; 95% CI 11.15-70.81). In contrast, tumor size was not associated with pathologic aggressive features on multivariate analysis (OR 0.81; 95% CI 0.54-1.22).
This study demonstrates that thyroid tumors expressing BRAF mutations correlate with aggressive pathologic features more than tumors expressing RAS-like mutations. When comparing tumors with BRAF and RAS-like mutations, the former were found to be smaller. As a result of this finding, this study suggests that molecular alterations may better predict aggressive pathologic features than the size of the tumor.
在临床实践中，甲状腺肿瘤大小在甲状腺恶性肿瘤分期以及应接受超声引导下细针穿刺的结节选择中起着关键作用。甲状腺肿瘤大小受肿瘤发生开始后的时间以及驱动生长的体细胞突变的影响，如与侵袭性表型相关的BRAF突变，以及与较惰性行为相关的RAS样突变。尽管大结节通常被认为更令人担忧，但肿瘤大小对预后的真正影响仍存在争议。本研究的目的是评估突变状态、肿瘤大小与侵袭性之间的关系，重点是BRAF和RAS样突变。
我们在加拿大蒙特利尔进行了一项多中心回顾性病历审查，纳入了2016年1月至2020年12月期间接受甲状腺手术、最终病理诊断为分化型甲状腺癌且进行了分子检测显示存在BRAF突变或RAS样突变（NRAS、HRAS或KRAS）的所有患者。
我们纳入了214例病例。其中BRAF突变病例117例（54.7%），RAS样突变病例97例（45.3%）。与RAS组相比，BRAF组的平均肿瘤大小在统计学上较小，分别为1.55厘米和2.04厘米。在多变量模型中，具有BRAF突变的肿瘤也更有可能表现出侵袭性病理特征，包括甲状腺外扩展、淋巴结转移、柱状细胞特征、高细胞组织学或鞋钉样组织学（比值比26.69；95%置信区间11.15 - 70.81）。相比之下，在多变量分析中肿瘤大小与病理侵袭性特征无关（比值比0.81；95%置信区间0.54 - 1.22）。
本研究表明，表达BRAF突变的甲状腺肿瘤比表达RAS样突变的肿瘤与侵袭性病理特征的相关性更强。在比较具有BRAF和RAS样突变的肿瘤时，发现前者较小。基于这一发现，本研究表明分子改变可能比肿瘤大小更能预测侵袭性病理特征。
