Concordance of BRAF V600E mutation between immunohistochemistry and genomic testing for thyroid cancer

Background BRAF V600E mutation is a significant therapeutic target for thyroid cancer, including anaplastic thyroid cancer (ATC). Although targeted therapy for this mutation requires genomic testing in Japan, turnaround time (TAT) is often unacceptably long, especially for certain conditions, such as ATC, which is one of the most aggressive cancers. Here, we evaluated concordance between immunohistochemistry (IHC) with a relatively short TAT of a few days and genomic testing in thyroid cancer. Methods Immunohistochemical staining was performed with BRAF (VE1) antibody (Ventana) using the OptiView method on samples already undergoing genomic testing. A pathologist blindly annotated each staining expression with a cut-off of 1% in the cytoplasm. We then calculated the positive percent agreement (PPA), negative percent agreement (NPA), and overall percent agreement (OPA). Results We identified 62 samples, including 12 of ATC, that underwent genomic testing using different methods: Oncomine Dx Target Test (ODxTT) (n = 32), MEBGEN BRAF 3 Kit (MEBGEN3) (n = 14), FoundationOne CDx (F1CDx) (n = 13), and GenMineTOP (TOP) (n = 1). Annotation results of IHC were positive for 31, negative for 29, and undeterminable for 2 samples due to low tumor content. PPA, NPA, and OPA were 100%, 91.7%, 96.9% for ODxTT; 100%, 100%, 100% for MEBGEN3; 100%, 80.0%, 93.9% for F1CDx; and incalculable, 100%, 100% for TOP, respectively. Discordance was found in the two undeterminable samples only. Conclusion Concordance between IHC and genomic testing in assessing BRAF V600E was encouragingly high; its reliability and potentially short TAT should benefit patients, especially those with ATC.