Age and BRAF^V600E Mutation Stratified Patients with Cytologically Benign Thyroid Nodules

Abstract

Purpose

Our objective was to evaluate the diagnostic performance of BRAF^V600E mutation for malignant, and to identify clinical characteristics associated with positive BRAF^V600E mutation in low-risk cytological and ultrasound diagnostic thyroid nodules. This aims to identify patients who may benefit from BRAF^V600E mutation testing and subsequent surgical intervention.

Patients and Methods

We analysis the clinical characteristics correlated with BRAF^V600E mutation in our detection cohort, including 204 patients with 217 thyroid nodules, and separate analyses were performed in 103 thyroid nodules with benign cytological result. Signaling pathway and immune response associated with age and BRAF^V600E mutation status were also evaluated in Asian patients with thyroid cancer from the Cancer Genome Atlas (TCGA) dataset.

Results

The positive BRAF^V600E mutation was significantly associated with higher Ultrasound (US) classification (p<0.001) and fine-needle aspiration (FNA) categories (p<0.001). BRAF^V600E mutation as a risk factor for malignancy, showing the optimal diagnostic efficacy for malignancy combined with FNA categories, with the AUC was 0.923. Otherwise, BRAF^V600E mutation is a risk factor in screening malignancy in low-risk FNA and US classification, which is significant correlation with patients age. Patients over 50 years old exhibiting a higher percentage of positive BRAF^V600E mutation when both ultrasound and FNA results indicate benign conditions, with higher risk of malignancy.

Conclusion

BRAF^V600E mutation is an accurate adjunctive diagnostic marker on FNA to screen malignancy. In low risk of both ultrasound and FNA results, the positive BRAF^V600E was significant increased in patients over 50 years old, which have higher risk of malignancy. Thus, the BRAF^V600E mutation detection and further surgery should be strengthened in older patients with benign cytological and US results thyroid nodules.

Keywords:

• thyroid nodule
• BRAF^V600E mutation
• benign cytology
• older
• diagnosis

Abbreviations

PTC, Papillary thyroid cancer; C-TIRADS, Chinese Thyroid imaging reporting and data system; TCGA, The Cancer Genome Atlas; FNA, Fine needle aspiration; US, Ultrasound; US-FNA, Ultrasound-guided fine needle aspiration; TBSRTC, The Bethesda System for Reporting Thyroid Cytopathology; MTC, Medullary thyroid cancer; DEGs, Different expression genes; KEGG, Kyoto Encyclopedia of Genes and Genomes; THCA, Thyroid carcinoma; AUC, Area under the curve; ATA, American Thyroid Association; PTMC, Papillary thyroid microcarcinoma; DOR, Diagnostic odds ratio; AJCC, American Joint Committee on Cancer.

Data Sharing Statement

The datasets supporting the conclusions of this article are included within the Supplementary Tables 1 and 2. The data generated in the present study may be requested from the corresponding author.

Ethics Approval and Consent to Participate

This study was conducted according to the guidelines of the Declaration of Helsinki. The study protocol was approved by the Ethics Institutional Review Board of The First Hospital of Putian City (approval number: 2023-066). The patients/participants provided their written informed consent to participate in this study.

Consent to Publication

The details of any images and tables can be published, and that the persons providing consent have been shown the article contents to be published, all authors agree with the publication.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The Authors declare that there is no conflict of interests.

Additional information

Funding

This research was funded by National Natural Science Foundation of China (grant number 92259101, 31771466) and Strategic Priority Research Program of the Chinese Academy of Sciences, China (grant number XDB38040100).