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Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-0987
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The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 12 6373-6379
Copyright © 2005 by The Endocrine Society

BRAF Mutation Predicts a Poorer Clinical Prognosis for Papillary Thyroid Cancer

Mingzhao Xing1, William H. Westra1, Ralph P. Tufano, Yoram Cohen, Eli Rosenbaum, Kerry J. Rhoden, Kathryn A. Carson, Vasily Vasko, Alexandr Larin, Giovanni Tallini, Sara Tolaney, Elizabeth H. Holt, Pei Hui, Christopher B. Umbricht, Shehzad Basaria, Marge Ewertz, Anthony P. Tufaro, Joseph A. Califano, Matthew D. Ringel, Martha A. Zeiger, David Sidransky and Paul W. Ladenson

Division of Endocrinology and Metabolism (M.X., S.T., M.E., P.W.L.), Department of Medicine, and Departments of Pathology (W.H.W.), Otolaryngology-Head and Neck Surgery (R.P.T., Y.C., E.R., J.A.C., D.S.), and Surgery (C.B.U., A.P.T., M.A.Z.), The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; J. B. Pierce Laboratory (K.J.R.), Department of Pathology (G.T., P.H.), and Section of Endocrinology-Department of Internal Medicine (E.H.H.), Yale University School of Medicine, New Haven, Connecticut 06510; Department of Pathology (G.T.), University of Bologna School of Medicine, 40126 Bologna, Italy; Department of Epidemiology (K.A.C.), the Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205; Washington Hospital Center and Medstar Research Institute (V.V.), Washington, D.C. 20010; Hospital for Endocrine Surgery (A.L.), 252000 Kiev, Ukraine; Division of Endocrinology and Metabolism (S.B.), The Johns Hopkins Bayview Medical Center, Baltimore, Maryland 21224; and Divisions of Endocrinology and Oncology (M.D.R.), The Ohio State University and Arthur G. James Cancer Center, Columbus, Ohio 43210

Address all correspondence and requests for reprints to: Mingzhao Xing, M.D., Ph.D., Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 333, Baltimore, Maryland 21287. E-mail: mxing1{at}jhmi.edu.

Context: Use of BRAF mutation in papillary thyroid cancer (PTC) has the potential to improve risk stratification of this cancer.

Objective: The objective of the study was to investigate the prognostic value of BRAF mutation in patients with PTC.

Design, Setting, and Subjects: In a multicenter study of 219 PTC patients, data on their clinicopathological characteristics and clinical courses between 1990 and 2004 were retrospectively collected, and their tumor BRAF mutation status was determined. Associations of BRAF mutation with initial tumor characteristics and subsequent recurrence were analyzed.

Main Outcome Measure: Relationships between the BRAF mutation status and clinicopathological outcomes, including recurrence, were measured.

Results: We found a significant association between BRAF mutation and extrathyroidal invasion (P < 0.001), lymph node metastasis (P < 0.001), and advanced tumor stage III/IV (P = 0.007) at initial surgery. This association remained significant on multivariate analysis, adjusting for conventional clinicopathological predictors of recurrence excluding the histological PTC subtype, but was lost when the tumor subtype was included in the model. BRAF mutation was also significantly associated with tumor recurrence, 25 vs. 9% with and without mutation, respectively (P = 0.004), during a median of 15 (interquartile range, 3–29) months of follow-up. This association remained significant on multivariate analysis adjusting for conventional clinicopathological predictors of recurrence, even including the PTC subtype (odds ratio, 4.0; 95% confidence interval, 1.1–14.1; P = 0.03). BRAF mutation was even an independent predictor of recurrence in patients with stage I/II disease, 22 vs. 5% with and without BRAF mutation, respectively (P = 0.002). BRAF mutation was also more frequently associated with absence of tumor I-131 avidity and treatment failure of recurrent disease.

Conclusions: In patients with PTC, BRAF mutation is associated with poorer clinicopathological outcomes and independently predicts recurrence. Therefore, BRAF mutation may be a useful molecular marker to assist in risk stratification for patients with PTC.




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Home page
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