Comparison of diagnostic methods for the detection of a BRAF mutation in papillary thyroid cancer

The most common genetic alteration identified in papillary thyroid cancer (PTC) encodes a valine to glutamic acid change at position 600 (V600E) in the BRAF proto-oncoprotein. The most accurate and reliable method for detecting this BRAF mutation has not yet been determined. In the present study, the sensitivity, specificity and feasibility of diagnostic methods for BRAF mutations were assessed. BRAF mutational analysis was performed by Sanger DNA sequencing, using the Cobas^® 4800 BRAF V600 test and by immunohistochemistry (IHC). A total of 185 tumor tissues samples were analyzed using the three assays. BRAF mutations were identified in 76.2% of samples by Sanger sequencing, 78.9% of samples by Cobas 4800 BRAF V600 test and 76.8% of samples by IHC. Complete concordance for the three methods was observed in 92.4% of samples. Sensitivity and specificity of Sanger sequencing were 97.2 and 95.2%. Sensitivity and specificity of the Cobas 4800 BRAF V600 test were 99.3 and 90.5%. Sensitivity and specificity of IHC were 98.6 and 97.6%. Furthermore, the presence of a BRAF mutation was significantly associated with extrathyroid extension and multifocality (P<0.05), but not associated with age, sex, lymph node metastasis, central node metastasis, lateral node metastasis, Tumor-Node-Metastasis stage or tumor size in patients with PTC. These results suggest that a combination of IHC and the Cobas 4800 BRAF V600 Test kit for V600E mutation analysis is the most efficient and reliable method in routine practice. Accurate screening for BRAF mutation may contribute to improving the risk stratification of PTC.