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. 2025 May 20;25(1):134.
doi: 10.1186/s12902-025-01954-9.

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

Thi Nhung Nguyen #  1 , Zhanna Mussazhanova #  1   2 , Hirokazu Kurohama  1 , Van Dong Hoang  3 , Ngoc Ha Le  4 , Thi Minh Hanh Ngo  5 , Van Phu Thang Nguyen  1 , Katsuya Matsuda  1 , Yuki Matsuoka  1 , Katsiaryna Tratsiakova  1 , Thi Ngoc Anh Nguyen  1 , Yerkezhan Sailaubekova  1 , Thi Phuong Nguyen  4 , Minh Son Le  5 , Masahiro Nakashima  6
Affiliations

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

Thi Nhung Nguyen et al. BMC Endocr Disord. .

Abstract

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.

Keywords: BRAF V600E; TERT promoter; Mitosis; Radioactive iodine refractory; Recurrent papillary thyroid carcinoma; Tall cell.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the principles of the Declaration of Helsinki. The study protocol was approved by the Institutional Review Board of the 108 Military Central Hospital (5199/GCN-BV) and the Institutional Ethical Committee for Medical Research at Nagasaki University (#15062617-6). Informed consent was obtained from all participants. Consent to publish: Not applicable. Competing interests: The authors declare no competing interests. Clinical trial number: Not applicable.

Figures

Fig. 1
Fig. 1
Receiver operating characteristic (ROC) curve analysis of mitosis count to predict radioactive iodine-refractory (RAI-R) cases. The optimal mitosis count was 1.5 to predict RAI-R with an area under the ROC curve (AUC) of 0.624, 95% confidence interval of 0.542 − 0.707, sensitivity of 32.6%, specificity of 89.7%, and Youden index of 0.223
Fig. 2
Fig. 2
Histological finding of loss of polarity/loss of cell cohesiveness (LOP/LCC) component in the invasive front area (hematoxylin–eosin). Scale bars indicated 120 μm. A, micropapillary B, solitary (arrowheads) and small nests (arrows). C, small nests
See this image and copyright information in PMC

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