Na Hee Young, Yu Hyeong Won, Kim Woochul, Moon Jae Hoon, Ahn Chang Ho, Choi Sang Il, Kim Yeo Koon, Choi June Young, Park So Yeon
Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.
Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
Clin Endocrinol (Oxf). 2022 Jul;97(1):106-115. doi: 10.1111/cen.14728. Epub 2022 Apr 5.
Mutations in the telomerase reverse transcriptase (TERT) promoter have been reported as a convincing prognostic factor in papillary thyroid carcinomas (PTCs). We aimed to investigate the frequency of TERT promoter mutations in patients with thyroid cancer and identify the clinicopathological factors associated with them in PTCs.
A total of 1086 consecutive cases of thyroid cancer composed of mostly PTCs were included in this study. TERT promoter and BRAF mutations were detected by pyrosequencing and their associations with clinicopathological features of tumour were analyzed.
TERT promoter mutations were observed in 1.9% of PTCs, 6.7% of follicular thyroid carcinomas, 8.3% of Hurthle cell carcinomas and 25.0% of poorly differentiated thyroid carcinomas and in a single case of anaplastic thyroid carcinoma. In PTCs, aggressive clinicopathological features, higher stage and BRAF V600E mutation were all found to be associated with TERT promoter mutations. Distant metastasis and disease recurrence were more frequent in TERT promoter-mutated PTCs. In multivariate analysis, age ≥55 years, tall cell variant, mitoses ≥3/10 high-power fields, tumour necrosis, and gross extrathyroidal extension (ETE) were identified as independent factors associated with TERT promoter mutations in PTCs.
This study revealed a relatively low frequency of TERT promoter mutations in Korean patients with PTC. Certain clinicopathological features including old age, tall cell variant, increased mitoses, tumour necrosis and gross ETE were found to be indicative of TERT promoter mutations in PTCs, suggesting that mutational analysis in a particular group of PTCs can be effective in regions with low mutation rates.
端粒酶逆转录酶（TERT）启动子突变已被报道为甲状腺乳头状癌（PTC）中一个有说服力的预后因素。我们旨在调查甲状腺癌患者中TERT启动子突变的频率，并确定PTC中与之相关的临床病理因素。
本研究纳入了总共1086例连续的甲状腺癌病例，其中大部分为PTC。通过焦磷酸测序检测TERT启动子和BRAF突变，并分析它们与肿瘤临床病理特征的相关性。
在1.9%的PTC、6.7%的甲状腺滤泡癌、8.3%的嗜酸性细胞癌、25.0%的低分化甲状腺癌以及1例未分化甲状腺癌中观察到TERT启动子突变。在PTC中，侵袭性临床病理特征、更高分期和BRAF V600E突变均与TERT启动子突变相关。TERT启动子突变的PTC远处转移和疾病复发更为频繁。多因素分析显示，年龄≥55岁、高细胞变异型、有丝分裂≥3/10高倍视野、肿瘤坏死以及肉眼可见的甲状腺外侵犯（ETE）是PTC中与TERT启动子突变相关的独立因素。
本研究显示韩国PTC患者中TERT启动子突变频率相对较低。某些临床病理特征，包括老年、高细胞变异型、有丝分裂增加、肿瘤坏死和肉眼可见的ETE，被发现可提示PTC中的TERT启动子突变，这表明在特定PTC患者群体中进行突变分析在突变率较低的地区可能是有效的。
