TERT 启动子突变的预后影响因与 BRAF 或 RAS 突变共存而增强，并通过 ATA 或 TNM 分期系统加强分化型甲状腺癌患者的风险预测。

Prognostic effects of TERT promoter mutations are enhanced by coexistence with BRAF or RAS mutations and strengthen the risk prediction by the ATA or TNM staging system in differentiated thyroid cancer patients.

机构信息

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Department of Internal Medicine, National Medical Center, Seoul, Korea.

出版信息

Cancer. 2016 May 1;122(9):1370-9. doi: 10.1002/cncr.29934. Epub 2016 Mar 11.

DOI:10.1002/cncr.29934

PMID:26969876

Abstract

BACKGROUND

Recent reports suggest that mutations in the promoter of the gene encoding telomerase reverse transcriptase (TERT) affect thyroid cancer outcomes.

METHODS

In all, 551 patients with differentiated thyroid cancer (DTC) enrolled in this study. The median follow-up duration was 4.8 years (interquartile range, 3.4-10.6 years).

RESULTS

TERT promoter mutations were detected in 25 DTCs (4.5%): 2.8% in neither BRAF-mutated nor RAS-mutated tumors, 4.8% in BRAF-mutated tumors, and 11.3% in RAS-mutated tumors. Moreover, they were frequently observed in American Thyroid Association (ATA) high-risk and TNM stage III/IV groups (9.1% and 12.9%, respectively). The coexistence of BRAF or RAS with TERT promoter mutations increased aggressive clinicopathologic features, recurrence (hazard ratio [HR] for BRAF, 4.64; 95% confidence interval [CI], 1.42-15.18; HR for RAS, 5.36; 95% CI, 1.20-24.02), and mortality (HR for BRAF, 15.13; 95% CI, 1.55-148.23; HR for RAS, 14.75; 95% CI, 1.30-167.00), even after adjustments for the age at diagnosis and sex, although the significance was lost after additional adjustments for pathologic characteristics. Furthermore, TERT promoter mutations significantly increased the risk of both recurrence and mortality in the ATA high-risk (HR for recurrence, 5.79; 95% CI, 2.07-16.18; HR for mortality, 16.16; 95% CI, 2.10-124.15) and TNM stage III/IV groups (HR for recurrence, 3.60; 95% CI, 1.19-10.85; HR for mortality, 9.06; 95% CI, 2.09-39.26).

CONCLUSIONS

The coexistence of BRAF or RAS mutations enhanced the prognostic effects of TERT promoter mutations. Furthermore, TERT promoter mutations strengthened the predictions of mortality and recurrence by the ATA and TNM staging systems, particularly for high-risk patients with DTC. Cancer 2016;122:1370-1379. © 2016 American Cancer Society.

摘要

背景

最近的报告表明，端粒酶逆转录酶（TERT）基因编码区启动子的突变影响甲状腺癌的结局。

方法

本研究共纳入 551 例分化型甲状腺癌（DTC）患者。中位随访时间为 4.8 年（四分位间距，3.4-10.6 年）。

结果

在 25 例 DTC 中检测到 TERT 启动子突变（4.5%）：BRAF 和 RAS 均未突变的肿瘤中为 2.8%，BRAF 突变的肿瘤中为 4.8%，RAS 突变的肿瘤中为 11.3%。此外，它们在甲状腺协会（ATA）高危和 TNM 分期 III/IV 组中常被观察到（分别为 9.1%和 12.9%）。BRAF 或 RAS 与 TERT 启动子突变的共存增加了侵袭性临床病理特征、复发（BRAF 的风险比[HR]为 4.64；95%置信区间[CI]为 1.42-15.18；RAS 的 HR 为 5.36；95%CI 为 1.20-24.02）和死亡率（BRAF 的 HR 为 15.13；95%CI 为 1.55-148.23；RAS 的 HR 为 14.75；95%CI 为 1.30-167.00），即使在调整诊断时的年龄和性别后也是如此，尽管在进一步调整病理特征后，这种相关性不再显著。此外，TERT 启动子突变显著增加了 ATA 高危（复发的 HR 为 5.79；95%CI 为 2.07-16.18；死亡的 HR 为 16.16；95%CI 为 2.10-124.15）和 TNM 分期 III/IV 组（复发的 HR 为 3.60；95%CI 为 1.19-10.85；死亡的 HR 为 9.06；95%CI 为 2.09-39.26）的复发和死亡风险。