Originally published as JCO Early Release 10.1200/JCO.2008.20.1426 on May 4 2009

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BRAF Mutation Testing of Thyroid Fine-Needle Aspiration Biopsy Specimens for Preoperative Risk Stratification in Papillary Thyroid Cancer

From the Division of Endocrinology and Metabolism, Departments of Medicine, Pathology, Surgery, and Otolaryngology-Head and Neck Surgery, the Johns Hopkins University School of Medicine; and Department of Epidemiology, the Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.

Corresponding author: Mingzhao Xing, MD, PhD, Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, 1830 E Monument St, Suite 333, Baltimore, MD 21287; e-mail: mxing1{at}jhmi.edu.

Purpose This study investigated the utility of BRAF mutation testing of thyroid fine-needle aspiration biopsy (FNAB) specimens for preoperative risk stratification in papillary thyroid cancer (PTC).

Patients and Methods We assessed the T1799A BRAF mutation status in thyroid FNAB specimens obtained from 190 patients before thyroidectomy for PTC and its association with clinicopathologic characteristics of the tumor revealed postoperatively.

Results We observed a significant association of BRAF mutation in preoperative FNAB specimens with poorer clinicopathologic outcomes of PTC. In comparison with the wild-type allele, BRAF mutation strongly predicted extrathyroidal extension (23% v 11%; P = .039), thyroid capsular invasion (29% v 16%; P = .045), and lymph node metastasis (38% v 18%; P = .002). During a median follow-up of 3 years (range, 0.6 to 10 years), PTC persistence/recurrence was seen in 36% of BRAF mutation–positive patients versus 12% of BRAF mutation–negative patients, with an odds ratio of 4.16 (95% CI, 1.70 to 10.17; P = .002). The positive and negative predictive values for preoperative FNAB-detected BRAF mutation to predict PTC persistence/recurrence were 36% and 88% for overall PTC and 34% and 92% for conventional PTC, respectively.

Conclusion Preoperative BRAF mutation testing of FNAB specimens provides a novel tool to preoperatively identify PTC patients at higher risk for extensive disease (extrathyroidal extension and lymph node metastases) and those who are more likely to manifest disease persistence/recurrence. BRAF mutation, as a powerful risk prognostic marker, may therefore be useful in appropriately tailoring the initial surgical extent for patients with PTC.

Supported by an R0-1 grant from the National Institutes of Health.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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