1 Department of Pathology, Konkuk University School of Medicine , Seoul, Korea.
2 Department of Pathology and Translational genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul, Korea.
Thyroid. 2017 Jun;27(6):802-810. doi: 10.1089/thy.2016.0547. Epub 2017 Apr 21.
The BRAF mutation in papillary thyroid carcinoma (PTC) is particularly prevalent in Korea, and a considerable number of wild-type BRAF PTCs harbor RAS mutations. In addition, subsets of other genetic alterations clearly exist, but their prevalence in the Korean population has not been well studied. Recent increased insight into noninvasive encapsulated follicular variant PTC has prompted endocrine pathologists to reclassify this entity as "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP). This study analyzed the genetic alterations among the histologic variants of PTC, including NIFTP.
Mutations of the BRAF and RAS genes and rearrangement of the RET/PTC1, NTRK1, and ALK genes using 769 preoperative fine-needle aspiration specimens and resected PTCs were analyzed.
Molecular alterations were found in 687 (89.3%) of 769 PTCs. BRAF mutation (80.8%) was the most frequent alteration, followed by RAS mutation and RET/PTC1, NTRK1, and ALK rearrangements (5.6%, 2.1%, 0.4%, and 0%, respectively). The low prevalence of NTRK1 fusions and the absence of an ALK fusion detected in Korea may also be attributed to the higher prevalence of the BRAF mutation. There were significant differences in the frequency of the genetic alterations among the histologic variants of PTC. The prevalence of NIFTP in PTC was 2.7%, and among the NIFTPs, 28.6% and 57.1% harbored BRAF and RAS mutations, respectively. Clinicopathologic factors and mutational profiles between NIFTP and encapsulated follicular variant PTC with capsular invasion group were not significantly different.
Genetic alterations in PTC vary among its different histologic variants and seem to be different in each ethnic group.
在甲状腺乳头状癌（PTC）中，BRAF 突变特别常见，并且相当数量的野生型 BRAF PTC 存在 RAS 突变。此外，显然存在其他遗传改变的亚群，但它们在韩国人群中的流行情况尚未得到很好的研究。最近对非侵袭性包膜滤泡变体 PTC 的深入了解促使内分泌病理学家将该实体重新分类为“具有乳头状核特征的非侵袭性滤泡性甲状腺肿瘤”（NIFTP）。本研究分析了包括 NIFTP 在内的 PTC 组织学变体中的遗传改变。
使用 769 例术前细针穿刺标本和切除的 PTC 分析了 BRAF 和 RAS 基因的突变以及 RET/PTC1、NTRK1 和 ALK 基因的重排。
在 769 例 PTC 中发现了分子改变 687 例（89.3%）。BRAF 突变（80.8%）是最常见的改变，其次是 RAS 突变和 RET/PTC1、NTRK1 和 ALK 重排（分别为 5.6%、2.1%、0.4%和 0%）。韩国 NTRK1 融合的低流行率和缺乏 ALK 融合可能也归因于 BRAF 突变的高流行率。PTC 的组织学变体之间的遗传改变频率存在显著差异。PTC 中 NIFTP 的患病率为 2.7%，在 NIFTP 中，分别有 28.6%和 57.1%携带 BRAF 和 RAS 突变。NIFTP 与有包膜侵犯的包膜滤泡变体 PTC 之间的临床病理因素和突变谱无显著差异。
PTC 的遗传改变在其不同的组织学变体中有所不同，并且在每个种族群体中似乎都不同。
