Association of Bethesda category and molecular mutation in patients
undergoing thyroidectomy
Abstract
Objective: 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.