Abstract
Objectives
The aim of this study was to ascertain the relationship between Bethesda category
and molecular mutation of thyroid nodules in patients undergoing thyroidectomy.
Design
A retrospective cohort of patients who underwent thyroidectomy following needle biopsy and molecular profile testing was performed.
Setting
Two tertiary care academic hospitals.
Participants
Consecutive patients with a dominant thyroid nodule who underwent both USFNA and molecular profile testing followed by thyroidectomy were included in the study.
Main Outcome and Measures
The main outcome was postoperative diagnosis of thyroid cancer and aggressivity of disease based on histopathological variants, nodal metastasis or extra-thyroidal extension. Associations between Bethesda category, molecular mutation and postoperative pathology was assessed using descriptive analysis and Chi-square testing.
Results
451 patients were included. 95.9% (93/97) of patients with a BRAFV600E mutation had a Bethesda category V or VI (P<0.001), and all had confirmed thyroid cancer on postoperative pathology. Those with H, K or N RAS or EIF1AX mutations, gene expression profiling (GEP) or copy number alterations showed an association with Bethesda categories III and IV (P≤0.01). Those with no identified molecular mutation had a lower incidence of aggressive thyroid cancer compared to those with an identified mutation (12.6% vs 44.3%, P<0.01).
Conclusion
BRAFV600E mutations were associated with thyroid cancer subtypes known to be more aggressive whereas RAS and EIF1AX mutations, copy number alterations, and GEP were related to Bethesda categories III and IV. These findings may help thyroid specialists better identify aggressive thyroid nodules associated with indeterminate Bethesda categories.
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