Immunohistochemistry cannot replace DNA analysis for evaluation of BRAF V600E mutations in papillary thyroid carcinoma

INTRODUCTION The BRAF V600E mutation is the most common genetic event occurring in papillary thyroid cancer (PTC). Recently, the possibility of using immunohistochemistry (IHC) to detect the BRAF V600E mutation has been reported. MATERIALS AND METHODS In 140 patients with classical PTC, the status of the BRAF V600E mutation was determined by IHC (using two alternative staining protocols, IHC-1 and IHC-2) and molecular biology methods: Sanger sequencing (SEQ) and real-time PCR (qPCR). RESULTS The BRAF V600E mutation was detected in 57.1% (80/140) patients by IHC-1 and 62.9% (88/140) patients by IHC-2. The highest correlation in detecting the BRAF V600E mutation was found between IHC-2 and qPCR (94.2%), and between IHC-1 and qPCR (83.9%). Correlations between IHC-1 and SEQ and between IHC-2 and SEQ were 71.5% and 76.2%, respectively. The IHC-2 protocol had higher sensitivity, PPV, and NPV, and Cohen's kappa than IHC- 1. The presence of BRAF V600E mutation in IHC-2 statistically correlated with age at diagnosis, histopathological stage, and extrathyroidal extension. CONCLUSIONS The results obtained in this study indicate a lack of concordance between BRAF V600E detection by IHC and molecular methods. The IHC method cannot replace molecular methods for the detection of the BRAF V600E mutation.