Stéphane Bardet1, Nicolas Goardon2, Justine Lequesne3, Dominique Vaur2, Renaud Ciappuccini4, Alexandra Leconte3, Hervé Monpeyssen5, Virginie Saguet-Rysanek6, Bénédicte Clarisse3, Audrey Lasne-Cardon7, Fabrice Ménégaux8, Laurence Leenhardt9, Camille Buffet9. 1. Department of Nuclear Medicine and Thyroid Unit, Centre François Baclesse, Caen, France. s.bardet@baclesse.fr. 2. Department of Molecular Biology, Centre François Baclesse, Caen, France. 3. Department of Clinical Research, Centre François Baclesse, Caen, France. 4. Department of Nuclear Medicine and Thyroid Unit, Centre François Baclesse, Caen, France. 5. Thyroid Unit, American Hospital, Neuilly sur Seine, France. 6. Department of Pathology, Centre François Baclesse, Caen, France. 7. Department of Head and Neck Surgery, Centre François Baclesse, Caen, France. 8. Department of Endocrine Surgery, Pitié Salpêtrière Hospital, IUC, University Paris VI, Paris, France. 9. Thyroid and Endocrine Tumors Unit, Institute of Endocrinology, Pitié Salpêtrière Hospital, IUC Sorbonne University, Paris, France.
Abstract
PURPOSE: The aim of this prospective study (ClinicalTrials.gov: NCT01880203) was to evaluate the diagnostic and prognostic value of a 7-panel mutation testing in the aspirates of thyroid nodules with indeterminate cytology (IC). METHODS: Eligible patients had a thyroid nodule ≥15 mm with IC (Bethesda III-V) for which surgery had been recommended. Detection of BRAF and RAS mutations was performed using pyrosequencing and RET/PTC and PAX8/PPARγ rearrangements using Real-Time quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Among 131 nodules with IC, 21 (16%) were malignant including 20 differentiated cancers and one thyroid lymphoma. Molecular abnormalities were identified in 15 nodules with IC corresponding to 10 malignant and 5 benign tumours. BRAF mutation was detected in 4 nodules all corresponding to classic PTC, and PAX8/PPARγ rearrangement in 2 HCC. In contrast, RAS mutation was identified in eight nodules, of which four were malignant, and one RET/PTC3 rearrangement in a follicular adenoma. This data resulted in an accuracy of 88%, sensitivity of 48%, specificity of 95%, positive-predictive value of 67%, and negative-predictive value of 91%. After a 56 month's follow-up, the proportion of excellent response was similar in patients with molecular alterations (67%) and those without (60%). CONCLUSIONS: By increasing the overall risk of cancer from 16 to 67% in mutated nodules and by diminishing it to 9% in wild-type, this study confirms the relevance of the 7-panel mutation testing in the diagnostic of nodules with IC. Genetic testing, however, did not predict outcome in the cancer patient subgroup.
PURPOSE: The aim of this prospective study (ClinicalTrials.gov: NCT01880203) was to evaluate the diagnostic and prognostic value of a 7-panel mutation testing in the aspirates of thyroid nodules with indeterminate cytology (IC). METHODS: Eligible patients had a thyroid nodule ≥15 mm with IC (Bethesda III-V) for which surgery had been recommended. Detection of BRAF and RAS mutations was performed using pyrosequencing and RET/PTC and PAX8/PPARγ rearrangements using Real-Time quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Among 131 nodules with IC, 21 (16%) were malignant including 20 differentiated cancers and one thyroid lymphoma. Molecular abnormalities were identified in 15 nodules with IC corresponding to 10 malignant and 5 benign tumours. BRAF mutation was detected in 4 nodules all corresponding to classic PTC, and PAX8/PPARγ rearrangement in 2 HCC. In contrast, RAS mutation was identified in eight nodules, of which four were malignant, and one RET/PTC3 rearrangement in a follicular adenoma. This data resulted in an accuracy of 88%, sensitivity of 48%, specificity of 95%, positive-predictive value of 67%, and negative-predictive value of 91%. After a 56 month's follow-up, the proportion of excellent response was similar in patients with molecular alterations (67%) and those without (60%). CONCLUSIONS: By increasing the overall risk of cancer from 16 to 67% in mutated nodules and by diminishing it to 9% in wild-type, this study confirms the relevance of the 7-panel mutation testing in the diagnostic of nodules with IC. Genetic testing, however, did not predict outcome in the cancerpatient subgroup.
Authors: Elizabeth J de Koster; Lioe-Fee de Geus-Oei; Adrienne H Brouwers; Eveline W C M van Dam; Lioe-Ting Dijkhorst-Oei; Adriana C H van Engen-van Grunsven; Wilbert B van den Hout; Tamira K Klooker; Romana T Netea-Maier; Marieke Snel; Wim J G Oyen; Dennis Vriens Journal: Eur J Nucl Med Mol Imaging Date: 2022-01-04 Impact factor: 10.057