Molecular testing of BRAF,RAS and TERT on thyroid FNAs with indeterminate cytology improves diagnostic accuracy |
| |
| Authors: | L Depaepe V Lapras M‐L Denier F Borson‐Chazot J‐C Lifante J Lopez |
| |
| Affiliation: | 1. Pathology department, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France;2. Radiology department, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France;3. Endocrinology department, Groupement hospitalier Est, Hospices Civils de Lyon, Bron, France;4. Endocrine surgery department, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France;5. Biochemistry and molecular biology department, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France;6. Cancer Research Center of Lyon, INSERM1052 CNRS5286, Université de Lyon, Lyon, France |
| |
| Abstract: | Objective Liquid‐based (LB)‐FNA is widely recognized as a reliable diagnostic method to evaluate thyroid nodules. However, up to 30% of LB‐FNA remain indeterminate according to the Bethesda system. Use of molecular biomarkers has been recommended to improve its pathological accuracy but implementation of these tests in clinical practice may be difficult. Here, we evaluated feasibility and performance of molecular profiling in routine practice by testing LB‐FNA for BRAF, N/HRAS and TERT mutations. Methods We studied a large prospective cohort of 326 cases, including 61 atypia of undetermined significance, 124 follicular neoplasms, 72 suspicious for malignancy and 69 malignant cases. Diagnosis of malignancy was confirmed by histology on paired surgical specimen. Results Mutated LB‐FNAs were significantly associated with malignancy regardless of the cytological classification. Overall sensitivity was 60% and specificity 89%. Importantly, in atypia of undetermined significance and follicular neoplasm patients undergoing surgery according to the Bethesda guidelines, negative predictive values were 85.4% and 90% respectively. TERT promoter mutation was rare but very specific for malignancy (5.5%) suggesting that it could be of interest in patients with indeterminate cytology. Conclusions Mutation profiling can be successfully performed on thyroid LB‐FNA without any dedicated sample in a pathology laboratory. It is an easy way to improve diagnostic accuracy of routine LB‐FNA and may help to better select patients for surgery and to avoid unnecessary thyroidectomies. |
| |
| Keywords: | indeterminate cytology molecular testing TERT promoter mutations thyroid cancer thyroid liquid‐based fine needle aspiration |
|
|
