Anti-BRAF V600E (Hu), ms clone HA01

Clone HA01 for BRAF V600E Histology

Clone HA01 reacts specifically with the BRAF V600E point mutation in tissue sections from routine formalin-fixed paraffin-embedded human tumors (IHC FFPE). This antibody has been validated for the identification of BRAF V600E positive cells in diverse human tumor tissues with an additional focus on neuropathological tissues selected according to WHO guidelines.

BRAF V600E as a Driver Mutation in Cancer

BRAF V600E is a well-established oncogenic driver mutation with broad clinical implications. Since first studies of BRAF mutations in cancers 2002 (1), BRAF V600E has evolved into a critical diagnostic, prognostic, and predictive tumor marker.

BRAF has been shown to be mutated in various types of cancers including malignant melanoma (~50%), papillary thyroid cancer (~45%), colorectal cancers (~10%) and has also been identified in ovarian, breast, and lung cancers (1,2,3). Several primary CNS neoplasms harbor a BRAF V600E mutation, e.g. several pediatric low-grade gliomas (4,5): ~60% of pleomorphic xanthoastrocytomas (PXA), 20–60% of gangliogliomas (GG), and roughly 10% of pilocytic astrocytomas.

BRAF – Function

Physiologically, BRAF acts a serine-threonine protein kinase and is a member of the RAF kinase family playing an important role in the RAS-RAF-MAPK signaling pathway, which regulates cell survival, proliferation and differentiation (6). 90% of oncogenic mutations in the BRAF gene are a single V600E substitution within the kinase domain and result in sustained kinase activity, constitutively activating the MAPK signaling pathway which leads to carcinogenesis (7,8).

References

1. Davies H et al. Mutations of the BRAF gene in human cancer. Nature 417:949-954, 2002
2. Dhomen N et al.BRAF signaling and targeted therapies in melanoma. Hematol Oncol Clin North Am 23:529-545, 2009
3. Xing M. BRAF mutation in thyroid cancer. Endocr Relat Cancer 12:245-262, 2005
4. Schindler G, Capper D et al. Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma. Acta Neuropathol.121(3):397-405, 2011.
5. Andrews LJ et al. Prevalence of BRAFV600 in glioma and use of BRAF Inhibitors in patients with BRAFV600 mutation-positive glioma: systematic review. Neuro-Oncology, 24(4):528-540, 2022
6. Wang XJ, Kim A, Li S. Immunohistochemical analysis using a BRAF V600E mutation specific antibody is highly sensitive and specific for the diagnosis of hairy cell leukemia. Int J Clin Exp Pathol. 7(7):4323-4328, 2014
7. Shinozaki E et al. Clinical significance of BRAF non-V600E mutations on the therapeutic effects of anti-EGFR monoclonal ab treatment in patients with pretreated metastatic colorectal cancer. Br JCancer 117(10):1450-1458, 2017
8. Tan YH, Liu Y, Eu KW, Ang PW, Li WQ, Salto-Tellez M, et al. Detection of BRAF V600E mutation by pyrosequencing. Pathology 40(3): 295-298, 2008