Endocrine Abstracts

Introduction: Thyroid nodules may be detected in up to 67% of the adult population and constitute big diagnostic challenge. Presurgical differentiation of follicular lesions between follicular adenoma (FA) and follicular thyroid carcinoma (FTC) is particularly difficult. Commercially available gene panels cover only a few, selected mutations to help in discrimination between FA and FTC. The aim of this study was to comprehensively assess the genetic background of thyroid follicular lesions and to find genetic alterations that are present solely in FTC and therefore may serve as malignancy determinants.

Material and methods: The material from 50 consecutive formalin-fixed, paraffin-embedded (FFPE) FA and FTC specimens were re-reviewed to confirm the diagnosis and to indicate the most appropriate part of the specimen for DNA sample collection. DNA was acquired from FFPE. The NGS sequencing on Ion PGM Sequencer (Thermo Fisher, USA) employing Ion AmpliSeq Cancer Hotspot Panel v2 was conducted. The obtained data from genomic experiments were subjected for analysis using dedicated software and compared with clinical data. In case when no alterations using Cancer Hotspot Panel was identified, an Ion AmpliSeq Comprehensive Cancer Panel was employed.

Results: The sequencing has revealed various mutations present only in case of FTC (but not in FA), which may serve as potential markers of malignancy of a follicular lesion, such as: APC, CTNNB1, EGFR, FBXW7, HBF1A, HNF1A, KRAS, NRAS, PIK3CA, TP53. The most common mutation was TP53. In the specimens of FA, JAK3, NOTCH1 and PDGFRA mutations were found. BRAF, KIT, PTEN and SMARCB1 were found in both FA and FTC, although were much more common in the latter. After extension of the gene panel to Comprehensive Cancer Panel we found that ARID1A, BLNK, MSH2 and SYNE1 were present only in FA, with the most frequent occurrence of BLNK mutation.

Conclusions: The results of our study demonstrate that FA and FTC may differ with detectable genetic alterations, which may support advanced follicular lesions diagnostics. Using wide gene panel including various mutations previously reported in different malignancies might be a good strategy to differentiate follicular thyroid lesions both preoperatively (to decide on therapy) and postoperatively (to confirm diagnosis in doubtful cases). Finding of new genes possibly participating in FTC pathways may enable searching for novel targeted therapeutic methods.