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In Reply We agree with Dr Xing that the analyses presented by Xing et al support an important biological role for BRAF V600E in promoting aggressive tumor behaviors. We disagree with Xing’s interpretation of the multivariable mortality analyses that included BRAF V600E status and PTC tumor behaviors (extrathyroidal invasion, lymph node metastases, and distant metastases) as predictors.
What these multivariable analyses showed was that when the BRAF V600E test result was examined together with aggressive tumor behaviors, BRAF V600E status was no longer independently associated with mortality. This multivariable model replicates the question confronting the clinician: what does knowledge of BRAF V600E status add to existing clinical staging? As we discussed in our Editorial, the analyses by Xing et al suggest that BRAF V600E testing does not contribute to the predictive value for PTC-related mortality beyond the information gleaned about aggressive tumor characteristics reported by a pathologist or radiological evaluation.
Cappola AR, Mandel SJ. BRAF V600E Mutation and Papillary Thyroid Cancer—In Reply. JAMA. 2013;310(5):535-536. doi:10.1001/jama.2013.8595