BRAFV600E and TERT promoter mutations and their impact on recurrent papillary thyroid carcinoma progression
Nhung N.T. Hoang V.D. Mussazhanova Z. Kurohama H. Ha L.N. Matsuda K. Nguyen V.P.T. Hanh N.T.M. Nguyen T.N.A. Nakashima M.
Jul 2025BioScientifica Ltd.
Endocrine Connections
2025#14Issue 7
Papillary thyroid carcinoma (PTC) is the most prevalent histological subtype of thyroid cancer. However, it remains unclear whether BRAFV600E, TERT promoter (TERT-p), and certain pathological markers, such as loss of polarity/loss of cell cohesiveness (LOP/LCC), tall cells, mitotic count, and Ki-67 labeling index (LI) in recurrent tumors, are associated with clinical outcomes in patients with PTC after reoperation for recurrent PTC. This study investigates the impact of BRAFV600E and TERT-p mutations on progression-free survival (PFS) after reoperation for recurrent PTC. Cox regression analysis was employed to identify parameters associated with PFS. During a mean follow-up period of 27 months after reoperation, 39 patients (21.3%) experienced disease progression. Coexistence of BRAFV600E and TERT-p mutations (double mutation: Dmut) was observed in 21.3% of patients. TERT-p, Dmut, LOP/LCC (≥10%), mitotic count (≥3per2mm2), and Ki-67 LI were found to be significantly associated with disease progression in unadjusted analyses. In a multivariable analysis, these associations remained significant, with hazard ratios and 95% confidence intervals for TERT-p, Dmut, LOP/LCC, mitotic count, and Ki-67 LI being 5.98 (2.31–15.5), 5.44 (2.21–13.3), 6.81 (2.00–23.2), 5.05 (2.07–12.3), and 5.85 (2.48–13.7), respectively. Extranodal extension was associated with disease progression in both unadjusted and multivariable analyses. TERT-p, Dmut, Ki-67 LI, LOP/LCC, mitotic count, and extranodal extension were identified as independent risk factors for poor PFS after reoperation. Close surveillance following reoperation is recommended for patients exhibiting these factors.
disease progression , loss of polarity/loss of cell cohesiveness , mitosis , recurrent papillary thyroid carcinoma , TERT
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Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Sakamoto, Japan
Medical Oncology Clinical Trial Unit Fiona Stanley Hospital, Murdoch, WA, Australia
Department of Fundamental Medicine, Al-Farabi Kazakh National University, Almaty, Kazakhstan
Department of Nuclear Medicine, 108 Military Central Hospital, Ha Noi, Viet Nam
Department of Pathology, 108 Military Central Hospital, Ha Noi, Viet Nam
Department of Tumor and Diagnostic Pathology
Medical Oncology Clinical Trial Unit Fiona Stanley Hospital
Department of Fundamental Medicine
Department of Nuclear Medicine
Department of Pathology
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