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Original Article
- TERT mutations and aggressive histopathologic characteristics of radioiodine-refractory papillary thyroid cancer
- Ju Yeon Pyo, Yoon Jin Cha, SoonWon Hong
- J Pathol Transl Med. 2024;58(6):310-320. Published online September 12, 2024
- DOI: https://doi.org/10.4132/jptm.2024.07.29
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Abstract
PDF - Background
Radioiodine (RI) ablation following thyroid-stimulating hormone suppression is an effective treatment for papillary thyroid cancer (PTC), typically leading to favorable outcomes. However, RI-refractory tumors exhibit aggressive behavior and poor prognoses. Recent studies highlight the role of genetic abnormalities in PTC signaling pathways, including the activation of telomerase reverse transcriptase (TERT), and the correlation of mutations with adverse outcomes.
Methods
This study analyzed mutations in BRAF V600E and the TERT-promoter genes, comparing clinicopathological features between RI-refractory and RI-responsive PTCs. Among 82 RI-refractory patients, formalin-fixed, paraffin-embedded tissues from initial surgeries were available for 26. Another 89 without distant metastasis over 5 years formed a matched RI-responsive control group.
Results
Histopathologically, RI-refractory PTCs showed increased frequencies of small tumor clusters without fibrovascular cores, hobnail features, and a high height-to-width ratio of tumor cells. These tumors were more likely to exhibit necrosis, mitosis, lymph node metastasis, extrathyroidal extension, and involvement of resection margins. TERT-promoter mutations were statistically significantly associated with these aggressive clinicopathologic features. Immunohistochemically, decreased expression of sodium iodide symporter and thyroglobulin stimulating hormone receptor proteins was common in RI-refractory PTCs, along with lower levels of oncogenic proteins such as vascular endothelial cell growth factor, vascular endothelial cell growth factor receptor 2, and nuclear factor kappa-light-chain-enhancer of activated B cells. Total loss of PTEN expression was occasionally observed. In contrast, all cases tested positive for cytoplasmic β-catenin.
Conclusions
RI-refractory PTCs are linked to TERT mutations and exhibit specific aggressive histopathologic features, particularly in tumor centers. -
Citations
Citations to this article as recorded by
- Characterizing thyroid carcinomas in the elderly: Histological subtypes and TERT promoter mutation analysis based on the latest WHO classification
Myoung Ju Koh, Songmi Noh, Jin Kyong Kim, Gi Jeong Kim
Annals of Diagnostic Pathology.2026; 80: 152578. CrossRef - The ability of anexelekto (AXL) expression and TERT promoter mutation to predict radioiodine-refractory differentiated thyroid carcinoma
Hasrayati Agustina, Tutik Nur Ayni, Yohana Azhar, Erwin Affandi Soeriadi, Bethy Suryawathy Hernowo
Diagnostic Pathology.2025;[Epub] CrossRef - Clinicopathologic characteristics of papillary thyroid carcinoma, tall cell subtype and subtype with tall cell features, an institutional experience
Xueting Jin, Shunsuke Koga, Xiao Zhou, Niaz Z. Khan, Zubair W. Baloch
Human Pathology.2025; 161: 105867. CrossRef - Calcifying nested stromal-epithelial tumor of the liver: Report of two cases revealing novel WT1 mutation and distinct epigenetic features
Andrea Strakova-Peterikova, Franco Fedeli, Boris Rychly, Jiri Soukup, Michael Michal, Petr Martinek, Marian Grendar, Elaheh Mosaieby, Nikola Ptakova, Maryna Slisarenko, Michal Michal, Kvetoslava Michalova
Virchows Archiv.2025;[Epub] CrossRef - Insulin resistance and metabolic dysfunction in thyroid nodules and differentiated thyroid cancer
Stefano Iuliano, Maria Mirabelli, Stefania Giuliano, Antonio Brunetti
Current Opinion in Oncology.2025;[Epub] CrossRef
- Characterizing thyroid carcinomas in the elderly: Histological subtypes and TERT promoter mutation analysis based on the latest WHO classification
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