Feasibility and performance of the Idylla™ NRAS/BRAF cartridge mutation assay on thyroid liquid‐based fine‐needle aspiration

• Published in: Diagnostic cytopathology 2021-12, Vol.49 (12), p.1265-1271
• Main Authors: Hamadou, Maud, Lopez, Jonathan, Benzerdjeb, Nazim, Cugnet‐Anceau, Christine, Schnoering, Gwenaelle, Besançon, Julie, Mezrag, Saliha, Lapras, Veronique, Denier, Marie‐Laure, Descotes, Françoise, Decaussin‐Petrucci, Myriam
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Biopsy, Fine-Needle; Cancer; DNA Mutational Analysis; Feasibility Studies; Female; GTP Phosphohydrolases - metabolism; Humans; Idylla; Life Sciences; Liquid Biopsy; liquid‐based fine‐needle aspiration; Male; Membrane Proteins - metabolism; Middle Aged; molecular testing; Mutation; Mutation - genetics; Proto-Oncogene Proteins B-raf - metabolism; Thyroid gland; Thyroid Gland - pathology; thyroid nodule; Young Adult
• ISSN: 8755-1039; 1097-0339
• DOI: 10.1002/dc.24897

Background Thyroid nodules with indeterminate cytology represent up to 30% of cases. Molecular testing is now highly recommended to improve management. This study aimed to evaluate the use of the Idylla™ NRAS/BRAF mutation test, a rapid and automated polymerase chain reaction (PCR) assay validated for fixed paraffin‐embedded use, on residual thyroid liquid‐based fine‐needle aspiration (LB‐FNA). Methods Concordance between mutations detected by the Idylla™ assay and the gold‐standard qPCR was assessed by splitting in two aliquots 31 BRAF or RAS mutated and 5 non‐mutated LB‐FNA samples. Samples were obtained either from simulated FNA after thyroidectomy or from FNA obtained during routine care. A third aliquot was used to assess the limit of detection of Idylla™ for five mutated samples. Results The Idylla™ assay showed a sensitivity of 97% and a specificity of 83% as results were concordant for 34 out of 36 samples. One discordant sample concerned a BRAF p.K601E‐mutation which is not detected by the Idylla™ cartridge. The other showed a false‐positive NRAS p.A146T detection and a weak BRAF p.V600E detection. The limit of detection of the Idylla™ assay was not reached by the dilution assay. Conclusion Idylla™ NRAS/BRAF mutation testing can be performed on residual thyroid LB‐FNA, using low DNA quantity input, thus not requiring a dedicated sample. The Idylla™ NRAS/BRAF assay offers a quick and easy first step for analyzing the main molecular alterations in indeterminate thyroid nodules, hence improving diagnostic management.