Biomaterial Database

Immunohistochemical detection of BRAF V600E mutant protein using the VE1 antibody in colorectal carcinoma is highly concordant with molecular testing but requires rigorous antibody optimization. 2014

Shih-Fan Kuan, and Sarah Navina, and Kristi L Cressman, and Reetesh K Pai

Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.

The BRAF V600E mutation occurs in 15% of colorectal carcinomas (CRCs) and has important genetic, prognostic, and therapeutic implications. A monoclonal antibody (VE1) targeting the BRAF V600E mutant protein has become available with variable efficacy in literature reports. We investigated the utility of the VE1 antibody in detecting BRAF V600E mutant protein in two cohorts: (1) a retrospectively accrued series of 103 resected CRCs with (N = 57) and without (N = 46) known BRAF V600E mutation status by PCR and (2) a prospective series of 25 CRCs requiring BRAF analysis during routine screening for Lynch syndrome. All 74 cases with positive BRAF V600E mutation demonstrated cytoplasmic positivity with the VE1 antibody with most tumors (70/74, 95%) demonstrating moderate to strong staining. Of the 54 BRAF V600E-negative cases, 51/54 CRCs (94%) were negative with the VE1 antibody while 3 CRCs (6%) demonstrated weak cytoplasmic staining. The sensitivity and specificity of VE1 was 100% and 94%, respectively. Ten BRAF V600E-mutated CRCs had adjacent precursor lesions including 7 sessile serrated adenomas associated with CRCs with high-level microsatellite instability (MSI-H). All 10 precursor adenomas were positive for VE1 staining with the 7 sessile serrated adenomas maintaining preserved MLH1 expression. Our results indicate that VE1 immunohistochemistry is a useful surrogate for the detection of the BRAF V600E mutation in CRC, although weak staining must be evaluated by BRAF PCR analysis to exclude a false positive result. In addition, the BRAF V600E mutation appears to be an early event before the divergent development into MSS and MSI-H pathways.

UI	MeSH Term	Description	Entries
D007150	Immunohistochemistry	Histochemical localization of immunoreactive substances using labeled antibodies as reagents.	Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D008967	Molecular Biology	A discipline concerned with studying biological phenomena in terms of the chemical and physical interactions of molecules.	Biochemical Genetics,Biology, Molecular,Genetics, Biochemical,Genetics, Molecular,Molecular Genetics,Biochemical Genetic,Genetic, Biochemical,Genetic, Molecular,Molecular Genetic
D003123	Colorectal Neoplasms, Hereditary Nonpolyposis	A group of autosomal-dominant inherited diseases in which COLON CANCER arises in discrete adenomas. Unlike FAMILIAL POLYPOSIS COLI with hundreds of polyps, hereditary nonpolyposis colorectal neoplasms occur much later, in the fourth and fifth decades. HNPCC has been associated with germline mutations in mismatch repair (MMR) genes. It has been subdivided into Lynch syndrome I or site-specific colonic cancer, and LYNCH SYNDROME II which includes extracolonic cancer.	Colon Cancer, Familial Nonpolyposis, Type 1,Colorectal Cancer, Hereditary Nonpolyposis, Type 1,Familial Nonpolyposis Colon Cancer Type 1,Hereditary Nonpolyposis Colorectal Cancer,Hereditary Nonpolyposis Colorectal Cancer Type 1,Hereditary Nonpolyposis Colorectal Neoplasms,Lynch Syndrome,Colon Cancer, Familial Nonpolyposis,Colorectal Cancer Hereditary Nonpolyposis,Familial Nonpolyposis Colon Cancer,Hereditary Nonpolyposis Colon Cancer,Lynch Cancer Family Syndrome I,Lynch Syndrome I,Syndrome, Lynch
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000236	Adenoma	A benign epithelial tumor with a glandular organization.	Adenoma, Basal Cell,Adenoma, Follicular,Adenoma, Microcystic,Adenoma, Monomorphic,Adenoma, Papillary,Adenoma, Trabecular,Adenomas,Adenomas, Basal Cell,Adenomas, Follicular,Adenomas, Microcystic,Adenomas, Monomorphic,Adenomas, Papillary,Adenomas, Trabecular,Basal Cell Adenoma,Basal Cell Adenomas,Follicular Adenoma,Follicular Adenomas,Microcystic Adenoma,Microcystic Adenomas,Monomorphic Adenoma,Monomorphic Adenomas,Papillary Adenoma,Papillary Adenomas,Trabecular Adenoma,Trabecular Adenomas
D000368	Aged	A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available.	Elderly
D000369	Aged, 80 and over	Persons 80 years of age and older.	Oldest Old