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microRNA 分类器在细胞学不确定的 RAS 突变甲状腺结节中的临床应用:一项多机构研究。

Clinical utility of a microRNA classifier in cytologically indeterminate thyroid nodules with RAS mutations: A multi-institutional study.

发表日期:2023 Oct 29
作者: Abhinay Tumati, Caitlin E Egan, Yeon J Lee-Saxton, Teagan E Marshall, Joyce Lee, Kavita Jain, Jonas J Heymann, Hamza Gokozan, Sara Abou Azar, Jason Schwarz, Xavier M Keutgen, Amanda M Laird, Toni Beninato, Rasa Zarnegar, Thomas J Fahey, Brendan M Finnerty
来源: MOLECULAR & CELLULAR PROTEOMICS

摘要:

分子检测指导细胞学不确定的甲状腺结节的治疗。我们评估了市售甲状腺突变组合加上 microRNA 风险分类器在对 RAS 突变结节进行分类时的实际临床效益。我们使用 ThyGenX/ThyGeNEXT-ThyraMIR 对 Bethesda III/IV 结节的分子检测结果进行了亚组分析2017 年至 2021 年间,在 3 个三级护理中心的平台上,将阳性结果定义为 10% 或更高的恶性肿瘤风险。我们从接受检测的 375 名患者(70.7% 女性,中位年龄 59.3 岁)中发现了 387 个结节。与阴性模块相比,阳性结节 (32.3%) 与手术干预次数增加 (74.4% vs 14.9%,P < .0001) 和手术病理学上的癌相关 (46.4% vs 3.4%,P < .0001)。 RAS 突变是最常见的突变,在 380 个结节中的 71 个(18.7%)中发现,并被分类为 ThyraMIR-(71 个结节中的 28 个;39.4%)或 ThyraMIR(71 个结节中的 43 个;60.6%)。在 RAS 突变结节中,ThyraMIR 组和 ThyraMIR- 组之间的手术率 (P = .2212) 或癌症诊断 (P = .6277) 以及敏感性、特异性、阴性预测值和阳性预测值没有显着差异ThyraMIR 的值分别为 64.7%、34.8%、40.0% 和 59.5%。尽管检测阳性与外科病理学中的恶性肿瘤相关,但 ThyraMIR 分类器无法区分良性和恶性 RAS 突变结节。无论 microRNA 表达状态如何,都应考虑对 RAS 突变结节进行诊断性肺叶切除术。版权所有 © 2023 Elsevier Inc. 保留所有权利。
Molecular testing guides the management of cytologically indeterminate thyroid nodules. We evaluated the real-world clinical benefit of a commercially available thyroid mutation panel plus microRNA risk classifier in classifying RAS-mutated nodules.We performed a subgroup analysis of the results of molecular testing of Bethesda III/IV nodules using the ThyGenX/ThyGeNEXT-ThyraMIR platform at 3 tertiary-care centers between 2017 and 2021, defining a positive result as 10% or greater risk of malignancy.We identified 387 nodules from 375 patients (70.7% female, median age 59.3 years) who underwent testing. Positive nodules (32.3%) were associated with increased surgical intervention (74.4% vs 14.9%, P < .0001) and carcinoma on surgical pathology (46.4% vs 3.4%, P < .0001) compared to negative modules. RAS mutations were the most common mutations, identified in 71 of 380 (18.7%) nodules, and were classified as ThyraMIR- (28 of 71; 39.4%) or ThyraMIR+ (43 of 71; 60.6%). Among RAS-mutated nodules, there was no significant difference in operative rate (P = .2212) or carcinoma diagnosis (P = .6277) between the ThyraMIR+ and ThyraMIR- groups, and the sensitivity, specificity, negative predictive value, and positive predictive value of ThyraMIR were 64.7%, 34.8%, 40.0%, and 59.5%, respectively.Although testing positive is associated with malignancy in surgical pathology, the ThyraMIR classifier failed to differentiate between benign and malignant RAS-mutated nodules. Diagnostic lobectomy should be considered for RAS-mutated nodules, regardless of microRNA expression status.Copyright © 2023 Elsevier Inc. All rights reserved.