Age and BRAFV600E Mutation Stratified Patients with Cytologically Benign Thyroid Nodules

Abstract

Abstract Background BRAF V600E mutation has high specificity in diagnosing papillary thyroid cancer (PTC) in benign cytological thyroid nodules. However, to avoid overdiagnosis and overtreatment, the BRAFV600E mutation detection was un-practical and not required immediately in benign cytology. A definitive diagnosis to distinguish positive BRAFV600E mutation in benign cytological results is desperately needed. Our objective was to identify the clinical characteristics associated with positive BRAFV600E mutation in cytologically benign thyroid nodules, which would allow to screen patients who may benefit from BRAFV600E mutation testing and further surgical intervention.Methods We analysis the clinical characteristics correlated with BRAFV600E mutation in our detection cohort, including 204 patients with 217 thyroid nodules, and separate analyses were performed in benign cytology and in patients with thyroid imaging reporting and data system (TI-RADS) classification 4a. Differential expression genes between positive and negative BRAFV600E mutation groups and older and younger age groups were assessed in Asian patients with thyroid cancer from the Cancer Genome Atlas (TCGA) dataset, and the association of age and BRAFV600E mutation with immune response were also evaluated.Results BRAF V600E mutations is a risk factor in screening malignancy in benign cytological classification, furthermore, the positive BRAFV600E mutation frequency was higher in patients older than 50 years (p = 0.0012) of cytologically benign thyroid nodules. Similarly, the positive BRAFV600E mutation was associated with patients age in TI-RADS classification 4a (p < 0.001), which ultrasound features could not provided predictive information for BRAFV600E mutation detection. BRAFV600E mutations as a risk factor for malignancy, had upregulated in advanced pathological T stage (p < 0.001) and N stage (p < 0.001) in TCGA-THCA cohort. And in thyroid nodules, BRAFV600E mutation was significantly associated with Ultrasound classification (p < 0.001) and fine needle aspiration (FNA) category (p < 0.001).Conclusions BRAF V600E mutation is an accurate adjunctive diagnostic marker on FNA to screen malignancy. In benign cytology, patients older than 50 years are more likely to have positive BRAFV600E mutation, which may associate with immune response and have higher risk of malignancy. Thus, the BRAFV600E mutation detection and further surgery should be strengthened in older patients with benign cytologically thyroid nodules.