BRAF is a MAPK/ERK signaling pathway kinase involved in regulating growth, proliferation, apoptosis and survival of cells. It is one of the most frequently somatically mutated genes in cancer, particularly in melanomas, thyroid carcinomas, and colorectal cancer. BRAF mutations (most frequently the V600E mutation) occur in up to 60% of melanomas and more than 60% of papillary thyroid carcinomas. BRAF mutation is also present in roughly 10% of colorectal cancers, where mutation detection is useful for differentiating CIMP (CpG Island Methylator Phenotype, BRAF V600E positive) from Lynch syndrome (typically BRAF mutation negative). Status of BRAF mutation will predict response to therapy in cases of advanced melanoma. Furthermore, BRAF-mutant tumors tend to be more aggressive and are linked with shorter survival. Thus, determining presence of BRAF mutation is an important step in the differential diagnosis of numerous malignancies. Staining of wild-type BRAF may be nuclear, cytoplasmic or membranous and is present in all tissues. References: Nature Biotechnology. 2016. 34 (2):155–63, PMID: 26619011; Endocr Relat Cancer. 2014 Jan 30;21(2):161-73, PMID: 24243688; Mod Pathol. 2018 Jan; 31(1): 24–38, PMID: 29148538; Am J Transl Res. 2018; 10(8): 2726–2736, PMID: 30210710; Molecular Cancer Therapeutics. 2011 Mar. 10 (3):385, DOI: 10.1158/1535-7163.MCT-10-0799