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. These findings may help
thyroid specialists better identify aggressive thyroid nodules
associated with indeterminate Bethesda categories.