The impact of C216T and hot spot mutations of the TERT promoter on the clinicopathologic characteristics and S100A10 expression in papillary thyroid carcinoma: a comparative study.

Abstract

Objective: 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.

Methods: 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.

Results: 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).

Conclusion: 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.