Molecular Testing for Mutations in Improving the Fine-Needle Aspiration Diagnosis of Thyroid Nodules

• Published in: The journal of clinical endocrinology and metabolism 2009-06, Vol.94 (6), p.2092-2098
• Main Authors: Nikiforov, Yuri E., Steward, David L., Robinson-Smith, Toni M., Haugen, Bryan R., Klopper, Joshua P., Zhu, Zhaowen, Fagin, James A., Falciglia, Mercedes, Weber, Katherine, Nikiforova, Marina N.
• Format: Article
• Language: English
• Subjects: Algorithms; Biological and medical sciences; Biopsy, Fine-Needle - methods; Cellular biology; Cytology; Diagnosis; Diagnosis, Differential; DNA Mutational Analysis - methods; Endocrinopathies; Feasibility Studies; Feeding. Feeding behavior; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; Humans; Malignancy; Medical sciences; Molecular Diagnostic Techniques - methods; Mutation; Nodules; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Patients; Pax8 protein; Peroxisome proliferator-activated receptors; Sensitivity and Specificity; Thyroid; Thyroid cancer; Thyroid gland; Thyroid Nodule - diagnosis; Thyroid Nodule - genetics; Thyroid Nodule - pathology; Thyroid Nodule - surgery; Thyroid. Thyroid axis (diseases); Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2009-0247

Context: Thyroid nodules are common in adults, but only a small fraction of them are malignant. Fine-needle aspiration (FNA) with cytological evaluation is the most reliable tool for cancer diagnosis in thyroid nodules. However, 10–40% of nodules are diagnosed as indeterminate by cytology, making it difficult to optimally manage these patients. Objective: The aim of this study was to establish the feasibility and role of testing for tumor-specific mutations in improving the FNA diagnosis of thyroid nodules. Design: The prospective study included 470 FNA samples of thyroid nodules from 328 patients. At the time of aspiration, a small portion of the material was collected and tested for BRAF, RAS, RET/PTC, and PAX8/PPARγ mutations. The mutational status was correlated with cytology and either surgical pathology diagnosis or follow-up (mean, 34 months). Results: A sufficient amount of nucleic acids were isolated in 98% of samples. Thirty-two mutations were found, including 18 BRAF, eight RAS, five RET/PTC, and one PAX8/PPARγ. The presence of any mutation was a strong indicator of cancer because 31 (97%) of mutation-positive nodules had a malignant diagnosis after surgery. A combination of cytology and molecular testing showed significant improvement in the diagnostic accuracy and allowed better prediction of malignancy in the nodules with indeterminate cytology. Conclusions: These results indicate that molecular testing of thyroid nodules for a panel of mutations can be effectively performed in a clinical setting. It enhances the accuracy of FNA cytology and is of particular value for thyroid nodules with indeterminate cytology. Testing for a panel of mutations in thyroid fine needle aspiration samples improves cancer detection, particularly in thyroid nodules with indeterminate cytology.