Background: Autoimmune thyroiditis (AIT), including Hashimoto's thyroiditis (HT) and Graves' disease (GD), frequently coexists with papillary thyroid carcinoma (PTC). Chronic inflammation may influence thyroid carcinogenesis; however, the relationship between AIT and aggressive molecular alterations in PTC, particularly BRAFV600E and TERT promoter mutations, remains unclear. Data from iodine-deficient regions such as Kazakhstan are limited.
Methods: We conducted a retrospective multicenter study of 231 patients with PTC from Kazakhstan treated between 2016 and 2020. Tumors were reclassified according to the World Health Organization 5th edition (2022). Clinicopathological characteristics, AIT status (HT and GD), BRAFV600E and TERT promoter mutation profiles, and proliferative activity (Ki-67) were analyzed. Associations between AIT, molecular alterations, and clinicopathological features were evaluated.
Results: Most patients were female (83.1%) and <55 years (68.4%). AIT disease was present in 55.3% of cases, predominantly HT, while GD was uncommon (3.3%). BRAFV600E mutation alone was detected in 64.0% of patients, BRAF/TERT promoter co-mutation in 5.2%, TERT promoter mutation alone in 1.9%, and no mutations in 28.9%. TERT promoter-related mutations, particularly BRAF/TERT promoter co-mutations, were significantly more frequent in patients without AIT (p = 0.029) and were associated with lymph node metastasis, advanced tumor stage, older age, and larger tumor size. Patients with AIT had fewer aggressive molecular alterations. Patients with GD had higher Ki-67 labeling index and more aggressive clinicopathological features.
Conclusions: Different AIT subtypes showed distinct molecular and clinicopathological patterns in PTC. HT tended to demonstrate fewer aggressive molecular features, whereas GD showed features suggestive of increased proliferative activity. A lower prevalence of TERT promoter-related mutations was observed in AIT-positive patients, suggesting possible differences in molecular aggressiveness. However, these findings require validation in larger cohorts with broader molecular profiling.
Copyright: © 2026 Kaidarova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.