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Background <p>Although papillary thyroid carcinomas (PTC) are usually indolent in nature and clinically controllable, two-thirds of metastatic diseases become radioactive iodine-refractory (RAI-R). This study aimed to determine the role of pathological features, <i>BRAF</i><sup><i>V600E</i></sup>, <i>TERT</i> promoter (<i>TERT</i>-p), and their combinations on Vietnamese patients with RAI-R recurrent PTC.</p> Methods <p>This cross-sectional study included 174 cases of locoregional recurrent PTC, including 135 and 39 RAI-R and RAI-avid (RAI-A) cases, respectively. Logistic regression analyses were used to evaluate the associations between pathological features, mutations, and RAI-R with tissues from recurrent lesions.</p> Results <p>Loss of polarity/loss of cell cohesiveness (LOP/LCC) component was exclusively observed in recurrent cancers in the RAI-R group. RAI-R was associated with <i>BRAF</i><sup><i>V600E</i></sup> mutation, <i>TERT</i>-p mutation, <i>BRAF</i><sup><i>V600E</i></sup>/<i>TERT</i>-p single mutant (Smut), <i>BRAF</i><sup><i>V600E</i></sup>/<i>TERT</i>-p double mutant (Dmut), tall cell component, and mitosis ≥ 2/2 mm<sup>2</sup> in the unadjusted logistic regression analysis. Multivariable logistic regression analysis revealed that <i>BRAF</i><sup><i>V600E</i></sup> mutation and Dmut were independent predictors of RAI-R. The presence of Dmut (odds ratio [OR] = 6.64) was more significantly associated with RAI-R compared with that of Smut (OR = 2.75). There was a marginal association between tall cell &gt; 5%, mitosis count ≥ 2/2 mm<sup>2</sup> and RAI-R. The combination of <i>BRAF</i><sup><i>V600E</i></sup>/tall cell components was the strongest predictor of RAI-R.</p> Conclusions <p>RAI-R PTC cases were independently associated with <i>BRAF</i><sup><i>V600E</i></sup>, Dmut. The association between Dmut and RAI-R PTC was stronger than that between Smut and RAI-R PTC. Future studies should focus on elucidating the role of mitotic count and LOP/LCC in RAI-R PTC.</p>

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Associations between pathological features and radioactive iodine-refractory recurrent papillary thyroid carcinoma: with mutation analysis using recurrent samples

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月20日

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  • Thi Nhung Nguyen,
  • Zhanna Mussazhanova,
  • Hirokazu Kurohama,
  • Van Dong Hoang,
  • Ngoc Ha Le,
  • Thi Minh Hanh Ngo,
  • Van Phu Thang Nguyen,
  • Katsuya Matsuda,
  • Yuki Matsuoka,
  • Katsiaryna Tratsiakova,
  • Thi Ngoc Anh Nguyen,
  • Yerkezhan Sailaubekova,
  • Thi Phuong Nguyen,
  • Minh Son Le,
  • Masahiro Nakashima

摘要

Background

Although papillary thyroid carcinomas (PTC) are usually indolent in nature and clinically controllable, two-thirds of metastatic diseases become radioactive iodine-refractory (RAI-R). This study aimed to determine the role of pathological features, BRAFV600E, TERT promoter (TERT-p), and their combinations on Vietnamese patients with RAI-R recurrent PTC.

Methods

This cross-sectional study included 174 cases of locoregional recurrent PTC, including 135 and 39 RAI-R and RAI-avid (RAI-A) cases, respectively. Logistic regression analyses were used to evaluate the associations between pathological features, mutations, and RAI-R with tissues from recurrent lesions.

Results

Loss of polarity/loss of cell cohesiveness (LOP/LCC) component was exclusively observed in recurrent cancers in the RAI-R group. RAI-R was associated with BRAFV600E mutation, TERT-p mutation, BRAFV600E/TERT-p single mutant (Smut), BRAFV600E/TERT-p double mutant (Dmut), tall cell component, and mitosis ≥ 2/2 mm2 in the unadjusted logistic regression analysis. Multivariable logistic regression analysis revealed that BRAFV600E mutation and Dmut were independent predictors of RAI-R. The presence of Dmut (odds ratio [OR] = 6.64) was more significantly associated with RAI-R compared with that of Smut (OR = 2.75). There was a marginal association between tall cell > 5%, mitosis count ≥ 2/2 mm2 and RAI-R. The combination of BRAFV600E/tall cell components was the strongest predictor of RAI-R.

Conclusions

RAI-R PTC cases were independently associated with BRAFV600E, Dmut. The association between Dmut and RAI-R PTC was stronger than that between Smut and RAI-R PTC. Future studies should focus on elucidating the role of mitotic count and LOP/LCC in RAI-R PTC.