BRAF Mutation Correlates with Aggressive Features, Little Predictive Value

Abstract

Objective: With widespread and sophisticated imaging techniques, micro papillary thyroid cancers (PTCs) may be discovered prior to developing the classic pathological determinants of aggressiveness, such as extrathyroidal extent (ETE). Many studies have suggested that the V600E B-Raf proto-oncogene (BRAF) mutation can be used as a marker for aggressive disease. One objective of this study is to determine what prognostic value this mutation holds. However, nearly all of current studies have focused solely on classically aggre ssive tumors, not classically nonaggressive samples. This study also seeks to determine the BRAF mutation status in both the groups of tumors. Materials and methods:Sixty-six PTC samples were tested for the V600E BRAF mutation using competitive allele-specific TaqMan probes in real-time PCR (Applied Biosystems/Life Technologies). Testing demonstrates that this assay has at least a <5% sensitivity to the mutation. Forty-five samples had at least one of four aggressive features. Samples with vascular invasion, ETE or lymph node metastasis (LNM) were also characterized as having poor prognosis. Results:The V600E BRAF mutation was found in 27 of the 45 aggressive samples (60.0%) and 5 of the 21 nonaggre ssive samples. The Fisher exact test resulted in a correlation between aggressiveness and BRAF mutation as well as corre lations between ETE, LNM and the BRAF mutation. When using the BRAF mutation as a predictor of prognosis based on the pathological features of aggressiveness, there was 60% sensitivity and 80% specificity. Conclusion:The V600E BRAF mutation is correlated with pathological aggressive features, but may lack sufficient specificity or sensitivity to be used as a marker to predict outcome.