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

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, BRAF^V600E, 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 BRAF^V600E mutation, TERT-p mutation, BRAF^V600E/TERT-p single mutant (Smut), BRAF^V600E/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 BRAF^V600E 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 BRAF^V600E/tall cell components was the strongest predictor of RAI-R.

Conclusions: RAI-R PTC cases were independently associated with BRAF^V600E, 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.