Department of Nuclear Medicine, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences and PUMC, Beijing, China; Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China.
Department of Pathology, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences and PUMC, Beijing, China.
Endocr Pract. 2022 Mar;28(3):265-270. doi: 10.1016/j.eprac.2021.12.005. Epub 2021 Dec 8.
To assess the impact of serine/threonine-protein kinase B-Raf (BRAF) V600E and telomerase reverse transcriptase (TERT) promoter mutations in patients with distant-metastatic differentiated thyroid cancer (DM-DTC) based on thyroglobulin (Tg) response to radioactive iodine (RAI) therapy.
The BRAF and TERT mutations in primary tumors or metastatic lymph nodes of 114 patients with DM-DTC were retrospectively examined. RAI avidity was evaluated using a posttreatment iodine-131 whole-body scan. The Tg response was dynamically assessed at a median follow-up period of 56.50 months (interquartile range, 28.43-97.98 months).
BRAF was detected in 38.6% of cases, the TERT mutation in 21.1% of cases, and both the BRAF and TERT mutations in 14.9% of cases. Patients with both the mutations tended to be older at diagnosis (P < .001) and less multifocal (P = .011) and have more aggressive histologic subtypes (P = .011) and a higher Ki-67 index (P = .003). Patients with neither mutation tended to be have more RAI avidity than those with either the BRAF mutation alone or both the mutations (P = .001 and .001, respectively). Patients with both the mutations exhibited a more unfavorable Tg response than those without both the mutations and those with the BRAF mutation alone (P = .001 and .013, respectively). The Tg progression-free survival was shorter in patients with the TERT mutation alone than in those with neither mutation (P = .021), and it tended to be shorter when it coexisted with the BRAF mutation (P < .001); however, no significant difference was observed between those with the BRAF mutation alone and those with neither mutation (P = .890).
The coexistence of the BRAF and TERT promoter mutations synergistically induce the loss of RAI avidity and leads to an undesirable Tg response in patients with DM-DTC. The TERT promoter mutation appears to affect Tg response more than the BRAF mutation.
根据放射性碘（RAI）治疗后甲状腺球蛋白（Tg）的反应，评估丝氨酸/苏氨酸蛋白激酶 B-Raf（BRAF）V600E 和端粒酶逆转录酶（TERT）启动子突变对远处转移性分化型甲状腺癌（DM-DTC）患者的影响。
回顾性分析 114 例 DM-DTC 患者原发肿瘤或转移淋巴结中的 BRAF 和 TERT 突变。采用治疗后碘-131 全身扫描评估 RAI 亲和力。在中位数为 56.50 个月（四分位距，28.43-97.98 个月）的随访期间，动态评估 Tg 反应。
38.6%的病例中检测到 BRAF，21.1%的病例中检测到 TERT 突变，14.9%的病例中同时检测到 BRAF 和 TERT 突变。同时存在两种突变的患者在诊断时往往年龄较大（P<0.001），且多灶性程度较轻（P=0.011），具有侵袭性更强的组织学亚型（P=0.011）和更高的 Ki-67 指数（P=0.003）。无两种突变的患者与仅有 BRAF 突变或同时存在两种突变的患者相比，更倾向于有更高的 RAI 摄取率（P=0.001 和 P=0.001）。同时存在两种突变的患者与无两种突变和仅有 BRAF 突变的患者相比，Tg 反应更不理想（P=0.001 和 P=0.013）。单独存在 TERT 突变的患者 Tg 无进展生存期短于无两种突变的患者（P=0.021），当与 BRAF 突变共存时，其无进展生存期更短（P<0.001）；然而，单独存在 BRAF 突变的患者与无两种突变的患者之间无显著差异（P=0.890）。
BRAF 和 TERT 启动子突变的共存协同诱导 RAI 摄取的丧失，并导致 DM-DTC 患者的 Tg 反应不理想。TERT 启动子突变对 Tg 反应的影响似乎大于 BRAF 突变。
