OR14-4 Does BRAF V600E Mutation Predict Aggressive Features in Classic Papillary Thyroid Cancer? Results from Four Endocrine Surgery Centers

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR14-Thyroid Cancer: Insights into Diagnosis & Treatment
Saturday, June 15, 2013: 11:30 AM-1:00 PM
Presentation Start Time: 12:15 PM
Room 103 (Moscone Center)
Carol Li*1, Patricia A. Han1, Kathleen C. Lee1, Louis C. Lee2, Amy C. Fox3, Toni Beninato4, Michele Thiess1, Thomas J. Sebo2, Geoffrey B Thompson2, Clive S. Grant2, Thomas J Giordano3, Paul G. Gauger3, Gerard M. Doherty3, Thomas J. Fahey III4, Justin Bishop1, James R. Eshleman1, Christopher B Umbricht1, Eric B. Schneider1 and Martha A. Zeiger1
1Johns Hopkins University School of Medicine, Baltimore, MD, 2Mayo Clinic, Rochester, MN, 3University of Michigan Health Systems, Ann Arbor, MI, 4Weill Cornell Medical Center, New York, NY
Does BRAF V600E Mutation Predict Aggressive Features in Classic Papillary Thyroid Cancer? Results from Four Endocrine Surgery Centers

Introduction: Existing evidence is controversial regarding the association between BRAF mutation status and central lymph node metastases (CLNM) in patients with papillary thyroid cancer (PTC) and therefore, whether to use BRAF as an indication for central lymph node dissection (CLND). Importantly, no study has incorporated multiple endocrine surgery practices that perform routine CLND for PTC and thus have patients who are truly evaluable for the presence of CLNM. 

Methods: Under IRB approval, consecutive patients with classical variant PTC who underwent total thyroidectomy and CLND as part of routine surgical practices at 4 tertiary endocrine surgery centers between January 2009 and December 2011 were retrospectively reviewed. BRAF mutation status was determined by pyrosequencing. Standard descriptive and bivariable analyses examined demographic, patient, and tumor-related factors. Multivariable logistic regression controlling for gender, age≥45, tumor size >2 cm, extrathyroidal extension (ETE), surgical margin involvement, lympho-vascular invasion (LVI) and multifocality examined the odds of CLNM associated with positive BRAF status.

Results:  A total of 315 individuals (70 males and 245 females) from the 4 centers, of whom 239 underwent prophylactic and 76 underwent therapeutic CLND were eligible for study.  253 (80.3%) patients were positive for the BRAF mutation.  59.3% of BRAF positive vs. 51.6% of BRAF negative patients had CLNM (p=0.27). Bivariable analysis also demonstrated no significant relationship between positive BRAF mutation and gender, age, tumor size, multifocality, LVI, surgical margin involvement, lateral lymph node metastasis, ETE, or TNM stage. In the multivariate analysis, positive BRAF mutation was not associated with CLNM. Multivariate analysis including only factors potentially available preoperatively (BRAF mutation, age, gender, and size) also showed no significant correlation between BRAFmutation and CLNM. 

Conclusion: This is the first multi-institutional study that included only patients who underwent CLND as part of routine surgical practice and examined the association of BRAF mutation status and aggressive features of PTC. Our results show that in patients with classical PTC, BRAF mutation is not an independent predictor of CLNM and therefore may not be useful for decisions regarding initial surgical management. Prospective studies are therefore needed before BRAF mutation analysis should be incorporated into a surgical algorithm.

Disclosure: MAZ: Principal Investigator, Veracyte, Inc.. Nothing to Disclose: CL, PAH, KCL, LCL, ACF, TB, MT, TJS, GBT, CSG, TJG, PGG, GMD, TJF III, JB, JRE, CBU, EBS

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm