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Comment & Response
June 15, 2017

When Somatic Mutations Are Associated With a Higher Aggressive Behavior—A Story of Announced Evidence

Author Affiliations
  • 1Division of Anatomic Pathology and Histology, Catholic University of the Sacred Heart, “Agostino Gemelli” School of Medicine, Rome
JAMA Oncol. Published online June 15, 2017. doi:10.1001/jamaoncol.2017.1510

To the Editor We read with interest the article by Liu et al1 concerning the prognostic value of the genetic duet of coexisting BRAF V600E and TERT promoter mutations in papillary thyroid cancer (PTC)-related mortality. We found some points in common on this challenging topic. According to the literature, the active debate concerning the diagnostic and prognostic role of somatic mutations and rearrangements, such as BRAF V600E, RET/PTC, or RAS mutations in PTC, has not been resolved.1,2 In fact, studies by Fugazzola et al3 and Puxeddu et al4 did not assess any significant association of BRAF V600E mutation with any of the common high-risk pathological characteristics and implication to the disease-free survival. However, in most of these series, the number of the cases examined was much smaller, ranging from 56 to 60, and several of them were conducted without subtype stratification of PTCs. This latter point might affect the percentage of genetic alteration because BRAF V600E mutation occurs mostly in conventional and tall-cell PTC and uncommonly in follicular-variant PTC, which represents a more favorable variant. However, several series, including ours, emphasized the correlationship between BRAF V600E and the more aggressive clinicopathological outcomes of conventional PTCs, especially in terms of extrathyroid infiltration and advanced stages.2,5 In fact, we confirmed a significant association between BRAF V600E mutation and aggressive histological parameters, such as bilaterality of PTCs (P < .001) and nodal involvement (P < .001), in our PTCs.2

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