TERT 启动子突变鉴定出无转移的晚期甲状腺癌中的高危人群。

TERT promoter mutations identify a high-risk group in metastasis-free advanced thyroid carcinoma.

机构信息

Hospices Civils de Lyon, Groupement Hospitalier Est, Service de Médecine Nucléaire, Bron Cedex, F-69677, France.

Hospices Civils de Lyon, Groupement Hospitalier Sud, Service de Biochimie et Biologie Moléculaire, Pierre Bénite, cedex, F-69495, France.

出版信息

Eur J Cancer. 2019 Feb;108:41-49. doi: 10.1016/j.ejca.2018.12.003. Epub 2019 Jan 12.

DOI:10.1016/j.ejca.2018.12.003

PMID:30648628

Abstract

BACKGROUND

TERT promoter mutations are associated with adverse clinicopathological characteristics in thyroid carcinomas and considered as a major indicator of poor outcomes. Nevertheless, most studies have pooled heterogeneous types of thyroid carcinomas and have been conducted retrospectively. We investigated the association between TERT promoter mutations and recurrence in a prospective series of 173 intermediate- to high-risk patients with thyroid cancer.

PATIENTS

Patients referred for radioiodine treatment after thyroidectomy for intermediate- to high-risk differentiated thyroid carcinoma were included in a prospective observational study and tested for TERT promoter, BRAF, and RAS mutations of their primary tumours. We analysed the relationship between TERT promoter mutations and outcomes.

RESULTS

The prevalence of TERT promoter mutations was 20.2% (35/173) in the total population. It was significantly higher in tumours harbouring aggressive histological features (poorly differentiated carcinoma, tall cell variant of papillary cancer or widely invasive follicular cancer) than in non-aggressive tumours: 32.7% (16/49) versus 15.3% (19/124; p = 0.020). TERT promoter mutations were also strongly associated with age ≥45 years (p = 0.005), pT4 stage (p = 0.015), metastatic disease (p = 0.014), and extrathyroidal extension (p = 0.002). TERT promoter mutations were associated with poor outcomes in the total population (p < 0.001) but not in the subgroup of non-metastatic patients (p = 0.051). However, they were associated with a worse outcome in patients both free of metastases and devoid of aggressive histological features. Neither BRAF nor RAS mutations were associated with event-free survival in non-metastatic patients.

CONCLUSION

Although their prognostic value does not seem to overcome that of histology, TERT promoter mutations may help to better define the prognosis of localized thyroid cancer patients without aggressive histology.

摘要

背景

TERT 启动子突变与甲状腺癌的不良临床病理特征相关，被认为是预后不良的主要指标。然而，大多数研究都汇集了不同类型的甲状腺癌，并进行了回顾性研究。我们在一项前瞻性系列研究中调查了 TERT 启动子突变与 173 例中高危甲状腺癌患者复发之间的关系。

患者

在中高危分化型甲状腺癌甲状腺切除术后接受放射性碘治疗的患者被纳入一项前瞻性观察性研究，并对其原发肿瘤的 TERT 启动子、BRAF 和 RAS 突变进行了检测。我们分析了 TERT 启动子突变与结局之间的关系。

结果

在总人群中，TERT 启动子突变的患病率为 20.2%（35/173）。在具有侵袭性组织学特征（低分化癌、甲状腺乳头状癌的高细胞变异型或广泛浸润性滤泡癌）的肿瘤中，TERT 启动子突变的发生率明显高于非侵袭性肿瘤：32.7%（16/49）与 15.3%（19/124；p=0.020）。TERT 启动子突变与年龄≥45 岁（p=0.005）、pT4 期（p=0.015）、转移性疾病（p=0.014）和甲状腺外延伸（p=0.002）也有强烈关联。TERT 启动子突变与总人群的不良结局相关（p<0.001），但与非转移性患者亚组无相关性（p=0.051）。然而，它们与无转移且无侵袭性组织学特征的患者的不良预后相关。在非转移性患者中，BRAF 或 RAS 突变与无事件生存无关。