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. 2025 Jun;30(6):1143-1151.
doi: 10.1007/s10147-025-02760-y. Epub 2025 Apr 10.

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

Ryutaro Onaga #  1   2 , Tomohiro Enokida #  1 , Shingo Sakashita  3   4 , Nobukazu Tanaka  1 , Yuta Hoshi  1 , Takuma Kishida  1 , Ryo Kuboki  1 , Takao Fujisawa  1 , Susumu Okano  1 , Hiroshi Nishino  2 , Makoto Ito  2 , Genichiro Ishii  5 , Shumpei Ishikawa  6 , Makoto Tahara  7
Affiliations

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

Ryutaro Onaga et al. Int J Clin Oncol. 2025 Jun.

Abstract

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.

Keywords: Anaplastic thyroid cancer; BRAF plus MEK inhibitors; CDx; IHC; Targeted therapy; Thyroid cancer.

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Conflict of interest statement

Declarations. Conflict of Interest: MT reports grants and personal fees from Ono Pharmaceutical and Bayer, and personal fees from MSD, BMS, Merck Biopharma, Novartis, Pfizer, Rakuten Medical, Lilly, Boehringer Ingelheim, Eisai, Chugai Pharmaceutical, Daiichi-Sankyo, Janssen Pharmaceutical, Genmab, Astra Zeneca, Abbvie and Astellas, outside the submitted work. SO reports personal fees from Ono Pharmaceutical, MSD, BMS, and Merck Biopharma outside the submitted work. TF reports honoraria for lectures from Amelieff Co. Ltd. GI reports grants from Takeda Pharmaceutical Company Limited, Noile-Immune Biotech, Indivumed GmbH, Sumitomo Dainippon Pharma Co., Ltd. Nihon Medi-Physics CO., Ltd. ONO PHARMACEUTICAL CO., LTD. DAIICHI SANKYO, INC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ethics Statement: This study protocol was approved by the Institutional Ethical Committee of the National Cancer Center Hospital East (reference number 2024-066). Written informed consent for participation was not required for this study, in accordance with national legislation and institutional requirements. Patients and their families were provided an opportunity to opt-out of the study in accordance with the policy of the Japanese government. The study was conducted in accordance with the principles laid down in the Declaration of Helsinki.

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