Molecular Testing for Somatic Mutations Improves the Accuracy of Thyroid Fine-needle Aspiration Biopsy
Thyroid fine-needle aspiration (FNA) biopsy is indeterminate or suspicious in up to 30% of cases and these patients are commonly subjected to at least a diagnostic hemithyroidectomy. If malignant on histology, a completion thyroidectomy is usually performed, which may be associated with higher morbidity. To determine the clinical utility of genetic testing in thyroid FNA biopsy, we conducted a prospective clinical trial.
Four hundred seventeen patients with 455 thyroid nodules were enrolled and had genetic testing for common somatic mutations (BRAF, NRAS, KRAS) and gene rearrangements (RET/PTC1, RET/PTC3, RAS, TRK1) by PCR and direct sequencing and by nested PCR, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of genetic testing in thyroid FNA biopsy were determined based on the histologic diagnosis.
One hundred twenty-five of 455 thyroid nodule FNA biopsies were indeterminate or suspicious on cytologic examination. Overall, 50 mutations were identified (23 BRAF, 4 RET/PTC1, 2 RET/PTC3, 21 NRAS) in the thyroid FNA biopsies. There were significantly more mutations detected in malignant thyroid nodules than in benign (P = 0.0001). For thyroid FNA biopsies that were indeterminate or suspicious, genetic testing had a sensitivity of 12%, specificity of 98%, PPV of 38%, and NPV of 65%.
Genetic testing for somatic mutations in thyroid FNA biopsy samples is feasible and identifies a subset of malignant thyroid neoplasms that are indeterminate or suspicious on FNA biopsy. Genetic testing for common somatic genetic alterations thus could allow for more definitive initial thyroidectomy in those with positive results.
- Mitchell JC, Parangi S (2004) Thyroid incidentalomas: a new epidemic. Curr Surg 61(6):545–551 CrossRef
- Yeh MW, Demircan O, Ituarte P et al (2004) False-negative fine-needle aspiration cytology results delay treatment and adversely affect outcome in patients with thyroid carcinoma. Thyroid 14(3):207–215 CrossRef
- Tan YY, Kebebew E, Reiff E et al (2007) Does routine consultation of thyroid fine-needle aspiration cytology change surgical management? J Am Coll Surg 205(1):8–12 CrossRef
- Shibru D, Chung KW, Kebebew E (2008) Recent developments in the clinical application of thyroid cancer biomarkers. Curr Opin Oncol 20(1):13–18 CrossRef
- Salvatore G, Giannini R, Faviana P et al (2004) Analysis of BRAF point mutation and RET/PTC rearrangement refines the fine-needle aspiration diagnosis of papillary thyroid carcinoma. J Clin Endocrinol Metab 89(10):5175–5180 CrossRef
- Cohen Y, Rosenbaum E, Clark DP et al (2004) Mutational analysis of BRAF in fine needle aspiration biopsies of the thyroid: a potential application for the preoperative assessment of thyroid nodules. Clin Cancer Res 10(8):2761–2765 CrossRef
- Rowe LR, Bentz BG, Bentz JS (2006) Utility of BRAF V600E mutation detection in cytologically indeterminate thyroid nodules. Cytojournal 3:10 CrossRef
- Jin L, Sebo TJ, Nakamura N et al (2006) BRAF mutation analysis in fine needle aspiration (FNA) cytology of the thyroid. Diagn Mol Pathol 15(3):136–143 CrossRef
- Sapio MR, Posca D, Raggioli A et al (2007) Detection of RET/PTC, TRK and BRAF mutations in preoperative diagnosis of thyroid nodules with indeterminate cytological findings. Clin Endocrinol (Oxf) 66(5):678–683 CrossRef
- Nikiforov YE, Steward DL, Robinson-Smith TM et al (2009) Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules. J Clin Endocrinol Metab 94(6):2092–2098 CrossRef
- Yip L, Nikiforova MN, Carty SE et al (2009) Optimizing surgical treatment of papillary thyroid carcinoma associated with BRAF mutation. Surgery 146(6):1215–1223 CrossRef
- Coyne C, Nikiforov YE (2010) RAS mutation-positive follicular variant of papillary thyroid carcinoma arising in a struma ovarii. Endocr Pathol 21(2):144–147 CrossRef
- Nikiforova MN, Nikiforov YE (2009) Molecular diagnostics and predictors in thyroid cancer. Thyroid 19(12):1351–1361 CrossRef
- Nam SY, Han BK, Ko EY et al (2010) BRAF V600E mutation analysis of thyroid nodules needle aspirates in relation to their ultrasonographic classification: a potential guide for selection of samples for molecular analysis. Thyroid 20(3):273–279 CrossRef
- Troncone G, Cozzolino I, Fedele M et al (2010) Preparation of thyroid FNA material for routine cytology and BRAF testing: a validation study. Diagn Cytopathol 38(3):172–176
- Filie AC, Asa SL, Geisinger KR et al (2008) Utilization of ancillary studies in thyroid fine needle aspirates: a synopsis of the National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference. Diagn Cytopathol 36(6):438–441 CrossRef
- Kebebew E, Peng M, Reiff E et al (2006) Diagnostic and extent of disease multigene assay for malignant thyroid neoplasms. Cancer 106(12):2592–2597 CrossRef
- Molecular Testing for Somatic Mutations Improves the Accuracy of Thyroid Fine-needle Aspiration Biopsy
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World Journal of Surgery
Volume 34, Issue 11 , pp 2589-2594
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- 1. Department of Surgery, University of California, San Francisco, CA, 94143, USA
- 2. Department of Pathology, University of California, San Francisco, CA, 94143, USA
- 3. Surgery Branch, National Cancer Institute, CRC Room 4-5952, 10 Center Drive, MSC 1201, Bethesda, MD, 20892-1201, USA