| Summary: | Testing for the <i>BRAF</i> mutation is mandatory for the management of patients with locally advanced or metastatic melanoma. Molecular analysis based on DNA sequencing remains the gold-standard method for the screening of the different <i>BRAF</i> mutations. These methods must be rapid, sensitive, and specific enough to allow optimal therapeutic management in daily practice and also to include patients in clinical trials. Here, we compared the Idylla <i>BRAF</i> Mutation Test and the anti-<i>BRAF V600E</i> (clone VE1) immunohistochemistry (IHC) in 90 melanoma samples, with a focus on a challenging cohort of 32 positive sentinel lymph nodes. The <i>BRAF</i> status was assessed with both methods independently of the percentage of tumor cells. The concordance rate was calculated excluding both non-contributory analyses and <i>BRAF</i><i>V600K/R/M</i> mutants due to the specific V600E-IHC test design. The incidence of the <i>BRAF</i><i>V600E</i> mutation was 33% with both <i>BRAF</i> Idylla and <i>BRAF</i> IHC. The agreement rate was 91% (72/79). Although the agreement rate was high, we suggest that the use of IHC is more suitable for rapid <i>BRAF</i> testing on sentinel lymph node biopsies when associated with a low percentage and scattered tumor cells, which gave a high risk of non-contributory analysis and/or false negative results with the Idylla<sup>TM</sup><i>BRAF</i> Mutation Test.
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