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The Prevalence and Prognostic Value of BRAF Mutation in Thyroid Cancer

Kebebew, Electron MD*†; Weng, Julie BS*; Bauer, Juergen MD†; Ranvier, Gustavo MD*; Clark, Orlo H. MD*†; Duh, Quan-Yang MD*; Shibru, Daniel MD*; Bastian, Boris MD†; Griffin, Ann PhD†

doi: 10.1097/SLA.0b013e318148563d
Original Articles

Objective: To examine the prevalence of BRAF mutation among thyroid cancer histologic subtypes and determine the association of BRAF mutation with indicators of poor prognosis for papillary thyroid cancer and patient outcome.

Summary Background Data: The appropriate extent of surgical treatment, adjuvant therapy and follow-up monitoring for thyroid cancer remains controversial. Advances in the molecular biology of thyroid cancer have helped to identify candidate markers of disease aggressiveness. A commonly found genetic alternation is a point mutation in the BRAF oncogene (BRAF V600E), which is primarily found in papillary thyroid cancer and is associated with more aggressive disease.

Methods: BRAF V600E mutation status was determined in 347 tumor samples from 314 patients with thyroid cancer (245 with conventional papillary thyroid cancer, 73 with follicular thyroid cancer, and 29 with the follicular variant of papillary thyroid cancer). Univariate and multivariate analyses were performed to determine the association of BRAF V600E with clinicopathologic factors and patient outcome.

Results: The prevalence of BRAF V600E mutation was higher in conventional papillary thyroid cancer (51.0%) than in follicular variant of papillary thyroid cancer (24.1%) and follicular thyroid cancer (1.4%) (P < 0.0001). In patients with conventional papillary thyroid cancer, BRAF V600E mutation was associated with older age (P = 0.0381), lymph node metastasis (P = 0.0323), distant metastasis (P = 0.045), higher TNM stage (I and II vs. III and IV, P = 0.0389), and recurrent and persistent disease (P = 0.009) with a median follow-up time of 6.0 years. Multivariate analysis showed that BRAF V600E mutation [OR (95% CI) = 4.2 (1.2–14.6)] and lymph node metastasis [OR (95% CI) = 7.75 (2.1–28.5)] were independently associated with recurrent and persistent disease in patients with conventional papillary thyroid cancer.

Conclusions: BRAF V600E mutation is primarily present in conventional papillary thyroid cancer. It is associated with an aggressive tumor phenotype and higher risk of recurrent and persistent disease in patients with conventional papillary thyroid cancer. Testing for this mutation may be useful for selecting initial therapy and for follow-up monitoring.

BRAF V600E mutation analysis was performed in 347 tumor samples from 314 patients with thyroid cancer (245 conventional papillary thyroid cancer, 73 follicular thyroid cancer, and 29 follicular variant of papillary thyroid cancer). The BRAF V600E mutation occurred almost exclusively in patients with conventional papillary thyroid cancer, in whom it was associated with aggressive tumor phenotype and a higher rate of recurrent and persistent disease.

From the Departments of *Surgery, and †Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.

Supported by the Robert Wood Johnson Foundation, American Cancer Society Research Scholars Grant, Hellman Family Grant, the University of California Cancer Research Committee, and the National Institutes of Health (NIH 1R21 CA 118688-01; to E.K.).

Reprints: Electron Kebebew, MD, FACS, University of California, San Francisco, Department of Surgery, Box 1674, UCSF/Mount Zion Medical Center, San Francisco, CA 94143-1674. E-mail: kebebewe@surgery.ucsf.edu.

© 2007 Lippincott Williams & Wilkins, Inc.