Different qualifiers of AUS/FLUS thyroid FNA have distinct BRAF, RAS, RET/PTC, and PAX8/PPARg alterations
Different qualifiers of AUS/FLUS thyroid FNA have distinct BRAF, RAS, RET/PTC, and PAX8/PPARg alterations
复制标题
DOI：
10.1002/cncy.21984
复制
发表时间：
2018-05-01
影响因子：
3.4
通讯作者：
Troncone, Giancarlo
中科院分区：
文献类型：
--
作者：
Bellevicine, Claudio;Sgariglia, Roberta;Troncone, Giancarlo
背景Bethesda系统用于报告未确定意义的非典型性/未确定意义的滤泡性病变类别(AUS/FUS)的甲状腺细胞病理类型，包括细针吸取(FNA)标本，这些标本不能直接分为良、恶性。为了确定基于非典型性限定词和分子检测的形态亚类分类是否可以改善AUS/FLOU患者的恶性风险分层，本研究评估了这些限定词与甲状腺肿瘤常见的分子改变之间的相关性。方法总共162例AUS/FLOU病例根据非典型性限定词(Hurthle细胞变化、建筑异型性和细胞学非典型性[CyA])进行亚类分类，并检测BRAF、N-H-KRAS、RET/PTC、结果突变阳性的AUS/FLU中SCyA的表达频率(37.84%)明显高于突变阴性的AUS/FLU(20/125，16.00%)；宝洁(P<；.0084)，并且它特别含有BRAFV600E点突变。在可获得的随访中证实为恶性肿瘤。相反，尽管RAS是在AUS/FUS FNA标本中发现的最常见的突变(37例中有26例[70.27%]；P<；0.0001)，但根据可用的随访，它分布在AUS/FUS的不同亚类中，并且与特定的非典型性限定因素或恶性结局没有明显的相关性。RET/PTC(n=1)和PAX8/PPARg(n=3)重排在FNA样本中很少被发现。结论SBRAF和RAS突变与不同的AUS/FUS限定子相关，因此具有不同的恶性风险。因此，混合分子和形态分类系统可以改善诊断为AUS/FLUS的甲状腺FNA样本的恶性风险分层。癌症细胞病理学2018；126：317-25。(C)2018年美国癌症学会。诊断限定词可以改善未确定意义的非典型性/未确定意义的毛囊病变病例的恶性肿瘤风险分层。在这里，报告了未确定意义的非典型性/未确定意义的毛囊病变与特定的基因组图谱之间的关联，这反过来又具有不同的阳性预测价值。
BACKGROUNDThe Bethesda System for Reporting Thyroid Cytopathology category of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) includes fine-needle aspiration (FNA) specimens that cannot straightforwardly be classified as benign or malignant. To determine whether morphological subcategorization based on atypia qualifiers and molecular testing could improve malignancy risk stratification of AUS/FLUS patients, this study assessed the correlation between these qualifiers and the molecular alterations commonly harbored by thyroid neoplasms.METHODSA total of 162 AUS/FLUS cases were subcategorized by atypia qualifiers (Hurthle cell changes, architectural atypia, and cytologic atypia [CyA]) and were tested for BRAF, N-H-KRAS, RET/PTC, and paired box 8 (PAX8)/peroxisome proliferator activated receptor (PPARg) mutations.RESULTSCyA was observed more frequently in mutation-positive AUS/FLUS (14 of 37 [37.84%]) than mutation-negative AUS/FLUS (20 of 125 [16.00%]; P < .0084), and it specifically harbored the BRAFV600E point mutation. Malignancy was confirmed in the available follow-up. Conversely, although RAS was the most frequent mutation identified in AUS/FLUS FNA specimens (26 of 37 cases [70.27%]; P < .0001), it was distributed across various AUS/FLUS subcategories and was not significantly associated with a specific atypia qualifier or malignant outcome according to the available follow-up. Rearrangements of both RET/PTC (n = 1) and PAX8/PPARg (n = 3) were rarely retrieved in the FNA samples.CONCLUSIONSBRAF and RAS mutations are associated with different AUS/FLUS qualifiers and hence have different risks of malignancy. Consequently, a hybrid molecular and morphological subcategorization system could improve the malignancy risk stratification of thyroid FNA samples diagnosed as AUS/FLUS. Cancer Cytopathol 2018;126:317-25. (c) 2018 American Cancer Society.Diagnostic qualifiers can improve the malignancy risk stratification of atypia of undetermined significance/follicular lesion of undetermined significance cases. Here an association is reported between atypia of undetermined significance/follicular lesion of undetermined significance qualifiers and specific genomic profiles, which in turn have different positive predictive values.