TERT mutations and aggressive histopathologic characteristics of radioiodine-refractory papillary thyroid cancer.

IF 1.7 Q3 PATHOLOGY
Ju Yeon Pyo, Yoon Jin Cha, SoonWon Hong
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引用次数: 0

Abstract

Background: Radioiodine (RI) ablation following thyroid-stimulating hormone suppression is an effective treatment for papillary thyroid cancer (PTC), typically leading to favorable outcomes. However, RI-refractory tumors exhibit aggressive behavior and poor prognoses. Recent studies highlight the role of genetic abnormalities in PTC signaling pathways, including the activation of telomerase reverse transcriptase (TERT), and the correlation of mutations with adverse outcomes.

Methods: This study analyzed mutations in BRAF V600E and the TERT-promoter genes, comparing clinicopathological features between RI-refractory and RI-responsive PTCs. Among 82 RI-refractory patients, formalin-fixed, paraffin-embedded tissues from initial surgeries were available for 26. Another 89 without distant metastasis over 5 years formed a matched RI-responsive control group.

Results: Histopathologically, RI-refractory PTCs showed increased frequencies of small tumor clusters without fibrovascular cores, hobnail features, and a high height-to-width ratio of tumor cells. These tumors were more likely to exhibit necrosis, mitosis, lymph node metastasis, extrathyroidal extension, and involvement of resection margins. TERT-promoter mutations were statistically significantly associated with these aggressive clinicopathologic features. Immunohistochemically, decreased expression of sodium iodide symporter and thyroglobulin stimulating hormone receptor proteins was common in RI-refractory PTCs, along with lower levels of oncogenic proteins such as vascular endothelial cell growth factor, vascular endothelial cell growth factor receptor 2, and nuclear factor kappa-light-chain-enhancer of activated B cells. Total loss of PTEN expression was occasionally observed. In contrast, all cases tested positive for cytoplasmic β-catenin.

Conclusions: RI-refractory PTCs are linked to TERT mutations and exhibit specific aggressive histopathologic features, particularly in tumor centers.

放射性碘难治性甲状腺乳头状癌的TERT突变和侵袭性组织病理学特征
背景:抑制促甲状腺激素后进行放射性碘(RI)消融是治疗甲状腺乳头状癌(PTC)的有效方法,通常能取得良好的疗效。然而,RI难治性肿瘤表现出侵袭性和不良预后。最近的研究强调了PTC信号通路中基因异常的作用,包括端粒酶逆转录酶(TERT)的激活,以及基因突变与不良预后的相关性:本研究分析了BRAF V600E和TERT启动子基因的突变,比较了RI难治性和RI反应性PTC的临床病理特征。在82例RI难治性患者中,有26例患者的福尔马林固定石蜡包埋组织来自初次手术。另有89名患者在5年内未发生远处转移,组成了相匹配的RI反应对照组:从组织病理学角度看,RI难治性PTC表现为无纤维血管核心的小肿瘤簇、梭形特征和肿瘤细胞高宽比增加。这些肿瘤更有可能出现坏死、有丝分裂、淋巴结转移、甲状腺外扩展和切除边缘受累。据统计,TERT-启动子突变与这些侵袭性临床病理特征有显著相关性。从免疫组化角度看,RI难治性PTC中常见碘化钠交感蛋白和甲状腺球蛋白刺激素受体蛋白表达减少,血管内皮细胞生长因子、血管内皮细胞生长因子受体2和活化B细胞核因子卡帕轻链增强子等致癌蛋白水平也较低。偶尔还能观察到 PTEN 表达的完全丧失。相反,所有病例的细胞质β-catenin检测结果均为阳性:RI难治性PTC与TERT突变有关,并表现出特殊的侵袭性组织病理学特征,尤其是在肿瘤中心。
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来源期刊
CiteScore
5.00
自引率
4.20%
发文量
45
审稿时长
14 weeks
期刊介绍: The Journal of Pathology and Translational Medicine is an open venue for the rapid publication of major achievements in various fields of pathology, cytopathology, and biomedical and translational research. The Journal aims to share new insights into the molecular and cellular mechanisms of human diseases and to report major advances in both experimental and clinical medicine, with a particular emphasis on translational research. The investigations of human cells and tissues using high-dimensional biology techniques such as genomics and proteomics will be given a high priority. Articles on stem cell biology are also welcome. The categories of manuscript include original articles, review and perspective articles, case studies, brief case reports, and letters to the editor.
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