Li Ping, Huang Chuqiang, Liu Xiaoling, Gui Huihui, Li Jian
Department of Pathology, Peking University Shenzhen Hospital, 1120 Lianhua Road, Shenzhen, 518036, Guangdong Province, China.
Department of Thyroid and Breast Surgery, Peking University Shenzhen Hospital, 1120 Lianhua Road, Shenzhen, 518036, Guangdong Province, China.
Diagn Pathol. 2025 Feb 11;20(1):15. doi: 10.1186/s13000-025-01613-6.
The C216T mutation in the TERT promoter (TERTp) is a rarely reported genetic alteration in papillary thyroid carcinoma (PTC). Its clinical significance remains unclear. This study aimed to compare the impact of the C216T and hot spot mutations (C228T and C250T) of TERTp on the clinicopathologic characteristics and the expression of S100A10, a member of the S100 protein family, in PTC.
In this retrospective study, a cohort comprising 8 PTC cases with the C216T mutation, 12 cases with the hot spot mutations, and 120 cases with the wildtype genotype was established. The influence of TERTp mutations on the clinicopathologic profiles of PTC was assessed.
The C216T mutation was mutually exclusive with the hot spot mutations and its frequency (0.19%) fell between that of C228T (0.68%) and C250T (0.06%). Compared to PTC cases with the wildtype genotype, cases with C216T mutations did not exhibit significant differences in clinicopathologic characteristics and S100A10 expression levels. In contrast, the hot spot mutations were positively associated with extrathyroidal extension (p = 0.001), ATA recurrence risk (p < 0.001), AJCC staging (p < 0.001), and increased expression of S100A10 (p = 0.005). Furthermore, a significant correlation was found between S100A10 expression and extrathyroidal extension (p = 0.005), lymph node metastasis (p = 0.013), and ATA recurrence risk (p = 0.023).
The C216T mutation did not induce the aggressiveness of PTC as the hot spot mutations did. Furthermore, the hot spot mutations were closely associated with the increased expression of S100A10. The latter may contribute to the pro-invasive effect of the hot spot mutations on PTC.
端粒酶逆转录酶启动子（TERTp）中的C216T突变是甲状腺乳头状癌（PTC）中一种鲜有报道的基因改变。其临床意义仍不明确。本研究旨在比较TERTp的C216T突变和热点突变（C228T和C250T）对PTC临床病理特征及S100蛋白家族成员S100A10表达的影响。
在这项回顾性研究中，建立了一个队列，包括8例具有C216T突变的PTC病例、12例具有热点突变的病例和120例具有野生型基因型的病例。评估TERTp突变对PTC临床病理特征的影响。
C216T突变与热点突变相互排斥，其频率（0.19%）介于C228T（0.68%）和C250T（0.06%）之间。与具有野生型基因型的PTC病例相比，具有C216T突变的病例在临床病理特征和S100A10表达水平上没有显著差异。相比之下，热点突变与甲状腺外侵犯（p = 0.001）、美国甲状腺协会（ATA）复发风险（p < 0.001）、美国癌症联合委员会（AJCC）分期（p < 0.001）以及S100A10表达增加（p = 0.005）呈正相关。此外，发现S100A10表达与甲状腺外侵犯（p = 0.005）、淋巴结转移（p = 0.013）和ATA复发风险（p = 0.023）之间存在显著相关性。
C216T突变不像热点突变那样诱导PTC的侵袭性。此外，热点突变与S100A10表达增加密切相关。后者可能有助于热点突变对PTC的促侵袭作用。
