%0 Journal Article
%T The Difference in Clinical Behavior of Gene Fusions Involving RET/PTC Fusions and THADA/IGF2BP3 Fusions in Thyroid Nodules.
%A Tali G
%A Payne AE
%A Hudson TJ
%A da Silva SD
%A Pusztaszeri M
%A Tamilia M
%A Forest VI
%J Cancers (Basel)
%V 15
%N 13
%D 2023 Jun 28
%M 37444504
%F 6.575
%R 10.3390/cancers15133394
%X BACKGROUND: Molecular testing has been used as an adjunct to morphological evaluation in the workup of thyroid nodules. This study investigated the impact of two gene fusions, RET/PTC and THADA/IGF2BP3, that have been described as oncogenic events in thyroid neoplasms.
METHODS: We performed a retrospective, single-centered study at a McGill University teaching hospital in Montreal, Canada, from January 2016 to August 2021. We included patients who underwent surgery for thyroid nodules that pre-operatively underwent molecular testing showing either RET/PTC or THADA/IGF2BP3 gene fusion.
RESULTS: This study included 697 consecutive operated thyroid nodules assessed using molecular testing, of which five had the RET/PTC fusion and seven had the THADA/IGF2BP3 fusion. Of the five nodules in the RET/PTC group, 100% were malignant and presented as Bethesda V/VI. Eighty percent (4/5) were found to have lymph node metastasis. Twenty percent (1/5) had extrathyroidal extensions. Sixty percent (3/5) were a diffuse sclerosing variant of papillary thyroid carcinoma, and the rest were the classical variant. Of the seven THADA/IGF2BP3 nodules, all presented as Bethesda III/IV and 71.4% (5/7) were malignant based on the final pathology analysis, and 28.6% (2/7) were NIFTP. All the THADA/IGF2BP3 fusion malignancies were a follicular variant of papillary thyroid carcinoma. None had lymph node metastasis or displayed extrathyroidal extensions.
CONCLUSIONS: RET/PTC nodules presented as Bethesda V/VI and potentially had more aggressive features, whereas THADA/IGF2BP3 nodules presented as Bethesda III/IV and had more indolent behavior. This understanding may allow clinicians to develop more targeted treatment plans, such as the extent of surgery and adjuvant radioactive iodine treatment.