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In Reply I disagree with Dr Ciarrocchi and colleagues that BRAF V600E has no role in the aggressiveness of PTC because of its dependence on tumor behaviors, including local and distant metastases and invasion. It is clear that PTC would not cause patient death without aggressive tumor behaviors.
Our study demonstrated a strong synergism between BRAF V600E and aggressive clinicopathological behaviors, as reflected by the strong synergy indices and the fact that the association of mortality with BRAF V600E or clinicopathological behavior alone was only moderate but increased when the 2 were considered jointly. Thus, BRAF V600E does have a significant association with mortality, which likely occurs through promoting aggressive tumor behaviors and would be misleadingly lost using conventional multivariable models. Further efforts are needed to define how to specifically use the prognostic value of BRAF V600E clinically.
Xing M. BRAF V600E Mutation and Papillary Thyroid Cancer—In Reply. JAMA. 2013;310(5):534-535. doi:10.1001/jama.2013.8598