Molecular Profiling of Papillary Thyroid Carcinoma in Korea with a High Prevalence of BRAFV600E Mutation
Molecular Profiling of Papillary Thyroid Carcinoma in Korea with a High Prevalence of BRAFV600E Mutation
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DOI：
10.1089/thy.2016.0547
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发表时间：
2017-06-01
期刊：
影响因子：
6.6
通讯作者：
Kim, Suk Kyeong
中科院分区：
文献类型：
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作者：
Lee, Seung Eun;Hwang, Tae Sook;Kim, Suk Kyeong
背景：BRAF(V600E)突变在韩国乳头状甲状腺癌(PTC)中尤为常见，相当数量的野生型BRAF PTC中存在RAS突变。此外，其他基因改变的亚群明显存在，但它们在韩国人群中的流行程度尚未得到很好的研究。最近对非侵袭性包裹性滤泡性变异型PTC的深入研究促使内分泌病理学家将其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)。这项研究分析了包括NIFTP在内的PTC组织变异体之间的遗传变化。方法：对769例术前细针吸取标本和切除的PTC标本进行BRAF、RAS基因突变和RET/PTC1、NTRK1、ALK基因重排分析。结果：769例PTC中有687例(89.3%)有分子改变。最常见的突变是BRAF(V600E)突变(80.8%)，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%)。在韩国检测到的NTRK1融合的低发生率和ALK融合的缺失也可能归因于BRAF(V600E)突变的较高发生率。不同组织学变异的PTC的基因改变频率有显著差异。NIFTP在PTC中的发生率为2.7%，在NIFTP中，BRAF和RAS突变的发生率分别为28.6%和57.1%。NIFTP组和包膜型卵泡变异型PTC伴包膜浸润组的临床病理因素和突变情况无显著差异。结论：PTC的遗传改变因其不同的组织学变异而不同，并且在每个种族中似乎是不同的。
Background: The BRAF(V600E) 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. Methods: 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. Results: Molecular alterations were found in 687 (89.3%) of 769 PTCs. BRAF(V600E) 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(V600E) 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. Conclusions: Genetic alterations in PTC vary among its different histologic variants and seem to be different in each ethnic group.