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Original Investigation |

Lack of Association of BRAF Mutation With Negative Prognostic Indicators in Papillary Thyroid Carcinoma:  The University of California, San Francisco, Experience

Christopher Gouveia, MD1,2; Nhu Thuy Can, MD3,4; Alan Bostrom, PhD1; James P. Grenert, MD, PhD3; Annemieke van Zante, MD, PhD3; Lisa A. Orloff, MD1
[+] Author Affiliations
1Department of Otolaryngology–Head and Neck Surgery, University of California, San Francisco, San Francisco
2Department of Otolaryngology–Head and Neck Surgery, Northwestern University, Chicago, Illinois
3Department of Anatomic Pathology, University of California, San Francisco, San Francisco
4Department of Pathology, University of Chicago, Chicago, Illinois
JAMA Otolaryngol Head Neck Surg. 2013;139(11):1164-1170. doi:10.1001/jamaoto.2013.4501.
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Importance  Papillary thyroid carcinoma (PTC) is the most common endocrine neoplasm. B-type raf kinase (BRAF) V600E mutation has been proposed as a negative prognostic indicator in PTC, and patients harboring it should receive more aggressive initial therapy.

Objective  To assess the significance of BRAF V600E mutation in PTC in the largest US sample to date.

Design  We identified patients from our institution’s pathology archives diagnosed as having PTC and meeting criteria for BRAF mutation testing. Medical records were analyzed for BRAF status (positive or negative) and a list of standardized clinicopathologic features.

Participants  A total of 429 patients with PTC at an academic medical center.

Main Outcomes and Measures  Clinicopathologic features in patients with PTC with and without BRAF mutation.

Results  Of 429 cases with PTC, 314 (73.2%) were positive for the BRAF mutation and 115 (26.8%) tested negative. BRAF mutation was significantly associated with tumor margin positivity (P = .03) and lymph node metastasis (P = .002) on univariate analysis but not on multivariate study. BRAF mutation was a predictor of male sex (odds ratio [OR], 3.2; 95% CI, 1.4-7.2), total thyroidectomy (OR, 2.6; 95% CI, 1.1-6.2), and a negative predictor of follicular variant PTC (OR, 0.1; 95% CI, 0.1-0.4). There was no significant association between BRAF positivity and tumor multicentricity, lymphovascular invasion, extranodal extension, central neck involvement, advanced stage (stage III or IV), and distant metastasis.

Conclusions and Relevance  BRAF V600E mutation has been extensively studied in relation to negative prognostic indicators in PTC, with no consistent relationship emerging. Two recent meta-analyses showed an overall association between BRAF status and aggressive disease features and called for tailoring treatment plans in patients accordingly. In this, the largest US study to date, BRAF status was not significantly associated with most clinicopathologic features suggestive of more aggressive disease.

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