Department of Otolaryngology - Head and Neck Surgery, Jewish General Hospital, McGill University, 3755 Ch. de la Côte-Sainte-Catherine Rd., Montreal, QC, H3T 1E2, Canada.
nt of Otolaryngology - Head and Neck Surgery, McGill University Health Centre, Montreal, QC, Canada.
J Otolaryngol Head Neck Surg. 2023 Feb 11;52(1):12. doi: 10.1186/s40463-022-00611-8.
Genomic testing has enhanced pre-surgical decision making for cytologically indeterminate thyroid nodules, but there remains uncertainty regarding RAS mutations. The addition of extra genetic alterations to previous driver mutation panels has been shown to improve predictive value. This study aims to evaluate the relationship between the mutant allele frequency (AF) and likelihood of malignancy in thyroid nodules with RAS mutations.
A retrospective cohort review was performed evaluating patients with indeterminate cytology (Bethesda categories III, IV and V) and ThyroSeq® v3 testing demonstrating a RAS mutation, who underwent surgery. Univariate and multivariate regression analyses were used to evaluate relationships between AF, other genetic alterations, and malignancy.
Thirty-nine patients met criteria, 77% of the thyroid nodules (30/39) were found to be malignant. None demonstrated aggressive pathology. On univariate regression, there was no relationship between AF and likelihood of malignancy. There was, however, a significant correlation between AF and the rate of an additional genetic alteration. Multivariate analysis found a trend between RAS, a second genetic alteration and malignancy, but it did not reach statistical significance.
There was no direct relationship between the level of allelic frequency in thyroid nodules expressing RAS mutations and the likelihood of malignancy. There was a statistically significant relationship between increasing AF and the presence of a second genetic abnormality, suggesting a possible progression from initial driver mutation and then a second genetic alteration prior to malignant transformation.
基因组检测增强了对细胞学不确定甲状腺结节的术前决策，但 RAS 突变仍然存在不确定性。向先前的驱动突变面板中添加额外的遗传改变已被证明可以提高预测值。本研究旨在评估 RAS 突变的甲状腺结节中突变等位基因频率 (AF) 与恶性肿瘤可能性之间的关系。
对经细胞学不确定（Bethesda 类别 III、IV 和 V）和 ThyroSeq® v3 检测显示 RAS 突变的患者进行了回顾性队列研究，这些患者接受了手术。使用单变量和多变量回归分析来评估 AF、其他遗传改变与恶性肿瘤之间的关系。
符合标准的 39 名患者，39 个甲状腺结节中的 77%（30/39）为恶性。无一例表现出侵袭性病理。在单变量回归中，AF 与恶性肿瘤的可能性之间没有关系。然而，AF 与额外遗传改变的发生率之间存在显著相关性。多变量分析发现 RAS、第二种遗传改变与恶性肿瘤之间存在趋势，但未达到统计学意义。
表达 RAS 突变的甲状腺结节中等位基因频率水平与恶性肿瘤的可能性之间没有直接关系。AF 升高与第二种遗传异常的存在呈统计学显著相关，这表明在恶性转化之前，可能存在从最初的驱动突变到第二种遗传改变的进展。
