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Negative reactions of BRAF mutation‐specific immunohistochemistry to non‐V600E mutations of BRAF
Author(s) -
Seto Katsutoshi,
Haneda Masataka,
Masago Katsuhiro,
Fujita Shiro,
Kato Seiichi,
Sasaki Eiichi,
Hosoda Waki,
Murakami Yoshiko,
Kuroda Hiroaki,
Horio Yoshitsugu,
Hida Toyoaki,
Okubo Kenichi,
Yatabe Yasushi
Publication year - 2020
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/pin.12903
Subject(s) - v600e , mutation , trametinib , dabrafenib , immunohistochemistry , cancer research , melanoma , lung cancer , medicine , mutation testing , pathology , biology , vemurafenib , gene , genetics , mapk/erk pathway , phosphorylation , metastatic melanoma
BRAF mutations are rare driver mutations in non‐small cell lung cancer (NSCLC), accounting for 1%–2% of the driver mutations, and the mutation spectrum has a wide range in contrast to other tumors. While V600E is a dominant mutation in melanoma, more than half of the mutations in NSCLCs are non‐V600E. However, treatment with dabrafenib plus trametinib targets the BRAF V600E mutation exclusively. Therefore, distinguishing between V600E and non‐V600E mutations is crucial for biomarker testing in NSCLC in order to determine treatment of choice. Immunohistochemistry (IHC) using the BRAF V600E mutation‐specific antibody is clinically used in melanoma patients, but little is known about its application in NSCLC, particularly with regard to the assay performance for non‐V600E mutations. In the present study, we examined 117 tumors with BRAF mutations, including 30 with non‐V600E mutations, using BRAF mutation‐specific IHC. None of the tumors with non‐V600E mutations, including two compound mutations, showed a positive reaction. Furthermore, all V600E mutations were positive except for one case with combined BRAF V600E and K601_W604 deletion. Our findings confirmed that the BRAF V600E mutation‐specific IHC is specific without any cross‐reactions to non‐V600E mutations, suggesting that this assay can be a useful screening tool in clinical practice.