Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
J Clin Invest. 2021 Sep 15;131(18). doi: 10.1172/JCI152696.
Papillary thyroid cancer (PTC) is the most common form of differentiated thyroid cancer in the pediatric population and represents the second most common malignancy in adolescent females. Historically, PTC has been classified on the basis of histology, however, accumulating data indicate that molecular subtyping based on somatic oncogenic alterations along with gene expression profiling can better predict clinical behavior and may provide opportunities to incorporate oncogene-specific inhibitory therapy to improve the response to radioactive iodine (RAI). In this issue of the JCI, Y.A. Lee, H. Lee, and colleagues showed that oncogenic fusions were more commonly associated with invasive disease, increased expression of MAPK signaling pathway genes (ERK score), and decreased expression of the sodium-iodine symporter, which was restored by RET- and NTRK-inhibitory therapy. These findings lend credence to the idea of reclassifying pediatric thyroid cancers using a three-tiered system, rather than the two-tiered adult system, and open avenues for the treatment of progressive, RAI-refractory PTC in patients.
甲状腺乳头状癌（PTC）是儿科人群中最常见的分化型甲状腺癌，也是青少年女性中第二常见的恶性肿瘤。历史上，PTC 是基于组织学进行分类的，然而，越来越多的数据表明，基于体细胞致癌改变和基因表达谱的分子亚型分类可以更好地预测临床行为，并可能为纳入针对致癌基因的抑制治疗以改善对放射性碘（RAI）的反应提供机会。在本期 JCI 中，Y.A. Lee、H. Lee 及其同事表明，致癌融合更常与侵袭性疾病相关，MAPK 信号通路基因（ERK 评分）的表达增加，钠碘同向转运体的表达减少，而 RET 和 NTRK 抑制性治疗可恢复该表达。这些发现为使用三层系统而不是两层成人系统对儿科甲状腺癌进行重新分类提供了依据，并为治疗进行性、RAI 难治性 PTC 患者开辟了新途径。
