Endocrine Abstracts

JOINT2901

Background: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, generally characterized by a good prognosis. However, a small percentage of PTCs demonstrates a higher aggressiveness and poor outcomes. Recent WHO 2022 classification of thyroid tumors introduced a group of differentiated high-grade thyroid carcinomas (DHGTC), along with poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid carcinomas (ATC) as advanced thyroid cancers. Due to the heterogeneity of diagnostic criteria and the rarity of the disease, molecular characterization of these tumors is needed.

Objectives: This is a single-center study investigating the presence of BRAFV600E and TERT promoter variants C228T and C250T in a group of patients routinely investigated for these genetic markers.

Materials and methods: All cases were successfully investigated by Sanger sequencing for the BRAFV600E, C228T and C250T TERT promoter variants using genomic DNA extracted from formalin-fixated paraffin-embedded (FFPE) tumor material.

Results: We included in the analysis a group of 23 patients (18-83 y) tested from 2023 to 2024 due to an adverse course of disease (loco-regional or distant metastases, radioiodine treatment resistance, high-risk histopathological features). After histopathological characterization, there were 13 DHGTC, 1 iefvPTC (invasive encapsulated follicular variant of papillary thyroid carcinomas), 4 PDTCs and 3 ATCs. We also included 2 patients with invasive PTC, molecularly tested in their nodular metastasis. The overall occurrence of BRAFV600E variant was 19/23 cases (82,6%). C228T was identified in 5/23 cases (21.7%). We did not identify C250T variant in any cases. Simultaneous presence of BRAFV600E and C228T was observed in 5 cases (3 PDTCs and 2 DHGTC). The co-occurrence of the variants was observed in patients older than 45 y.o, except for one patient of 32 y.o, with nodular metastasis and invasive PTC. Another patient had both variants in microPTC, coexisting with a medullary thyroid carcinoma on the same lobe.

Conclusions: A proper molecular stratification is crucial to select the group of patients at high risk of unfavorable PTC course and simultaneously to avoid overtreatment in low-risk cases.