BRAFV600E and TERT promoter mutations and their impact on recurrent papillary thyroid carcinoma progression

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...

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Main Authors: Nguyen Thi Nhung, Van Dong Hoang, Zhanna Mussazhanova, Hirokazu Kurohama, Le Ngoc Ha, Katsuya Matsuda, Van Phu Thang Nguyen, Ngo Thi Minh Hanh, Thi Ngoc Anh Nguyen, Masahiro Nakashima
Format: Article
Language:English
Published: Bioscientifica 2025-07-01
Series:Endocrine Connections
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Online Access:https://ec.bioscientifica.com/view/journals/ec/14/7/EC-25-0116.xml
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author Nguyen Thi Nhung
Van Dong Hoang
Zhanna Mussazhanova
Hirokazu Kurohama
Le Ngoc Ha
Katsuya Matsuda
Van Phu Thang Nguyen
Ngo Thi Minh Hanh
Thi Ngoc Anh Nguyen
Masahiro Nakashima
author_facet Nguyen Thi Nhung
Van Dong Hoang
Zhanna Mussazhanova
Hirokazu Kurohama
Le Ngoc Ha
Katsuya Matsuda
Van Phu Thang Nguyen
Ngo Thi Minh Hanh
Thi Ngoc Anh Nguyen
Masahiro Nakashima
author_sort Nguyen Thi Nhung
collection DOAJ
description 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 (≥3 per 2 mm2), 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.
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spelling doaj-art-e74df8f8e4c24df285a7abc9ba2c19ce2025-08-20T02:56:39ZengBioscientificaEndocrine Connections2049-36142025-07-0114710.1530/EC-25-01161BRAFV600E and TERT promoter mutations and their impact on recurrent papillary thyroid carcinoma progressionNguyen Thi Nhung0Van Dong Hoang1Zhanna Mussazhanova2Hirokazu Kurohama3Le Ngoc Ha4Katsuya Matsuda5Van Phu Thang Nguyen6Ngo Thi Minh Hanh7Thi Ngoc Anh Nguyen8Masahiro Nakashima9Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto, Nagasaki, JapanMedical Oncology Clinical Trial Unit Fiona Stanley Hospital, Murdoch, Western Australia, AustraliaDepartment of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto, Nagasaki, JapanDepartment of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto, Nagasaki, JapanDepartment of Nuclear Medicine, 108 Military Central Hospital, Ha Noi, VietnamDepartment of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto, Nagasaki, JapanDepartment of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto, Nagasaki, JapanDepartment of Pathology, 108 Military Central Hospital, Ha Noi, VietnamDepartment of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto, Nagasaki, JapanDepartment of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto, Nagasaki, JapanPapillary 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 (≥3 per 2 mm2), 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.https://ec.bioscientifica.com/view/journals/ec/14/7/EC-25-0116.xmlrecurrent papillary thyroid carcinomadisease progressiontertloss of polarity/loss of cell cohesivenessmitosis
spellingShingle Nguyen Thi Nhung
Van Dong Hoang
Zhanna Mussazhanova
Hirokazu Kurohama
Le Ngoc Ha
Katsuya Matsuda
Van Phu Thang Nguyen
Ngo Thi Minh Hanh
Thi Ngoc Anh Nguyen
Masahiro Nakashima
BRAFV600E and TERT promoter mutations and their impact on recurrent papillary thyroid carcinoma progression
Endocrine Connections
recurrent papillary thyroid carcinoma
disease progression
tert
loss of polarity/loss of cell cohesiveness
mitosis
title BRAFV600E and TERT promoter mutations and their impact on recurrent papillary thyroid carcinoma progression
title_full BRAFV600E and TERT promoter mutations and their impact on recurrent papillary thyroid carcinoma progression
title_fullStr BRAFV600E and TERT promoter mutations and their impact on recurrent papillary thyroid carcinoma progression
title_full_unstemmed BRAFV600E and TERT promoter mutations and their impact on recurrent papillary thyroid carcinoma progression
title_short BRAFV600E and TERT promoter mutations and their impact on recurrent papillary thyroid carcinoma progression
title_sort brafv600e and tert promoter mutations and their impact on recurrent papillary thyroid carcinoma progression
topic recurrent papillary thyroid carcinoma
disease progression
tert
loss of polarity/loss of cell cohesiveness
mitosis
url https://ec.bioscientifica.com/view/journals/ec/14/7/EC-25-0116.xml
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