GENETIC TESTING OF FINE-NEEDLE ASPIRATION BIOPSY FOR DIAGNOSIS OF THYROID CANCER

Curitiba

Congreso; XIX Latin American Thyroid Congress; 2023

Sociedad Latinoamericana de Tiroides

Introduction: The frequency of palpable thyroid nodules is ~5% in the population, but only a small fraction of them are malignant(thyroid cancer). Fine-needle aspiration biopsy (FNAB) is the most reliable tool for malignant thyroid nodule screening. However,indeterminate thyroid nodules are diagnosed in up to 30% of fine‐needle aspirations and the risk of malignancy in these cases are highlyvariable. The understanding of the molecular events that promote thyroid cancer has allowed a substantial theranostic improvementof thyroid nodules. Particularly, genetic testing for proto-oncogene mutations has improved the diagnostic accuracy of indeterminatethyroid nodules. Objective: To develop a PCR-based proto-oncogene genetic testing including the analysis of point mutations andgene fusions to improve the theranostic of thyroid cancer. Methods: Point mutations in the proto-oncogenes BRAF codons 600 and601 and H/N/KRAS codons 12, 13 and 61 were assessed using Sanger sequencing. Gene fusion involving the proto-oncogenesRET, NTRK, ALK, BRAF and PPARγ were investigated using multiplex PCR. Results: Genetic testing was conducted in a pilotretrospective study including 26 FNAB samples with cytological analysis classified according to Bethesda system as benign (n = 8)or suggestive of malignancy (n = 18). Genomic DNA and total RNA from residual material from FNAB samples was isolated. Thepoint mutations p.V600E BRAF (n = 12) and p.G12V HRAS (n = 1), and the gene fusions RET/PTC1 (n = 2) and ETV6-NTRK3(n = 1) were detected in FNAB samples suggested of malignancy. The presence of mutation was a strong indicator of cancer asanatomopathological analysis after surgery indicated thyroid cancer in all oncogene-positive nodules. Conclusion: Clinically-applicablegenetic testing showed significant advance in the diagnostic accuracy of malignancy in the nodules, improving presurgical malignancyrisk assessment in order to avoid unnecessary diagnostic surgeries. Moreover, genetic testing allow to design personalized managementof patients with thyroid cancer.