Detection of the BRAFV600E protein in human colon carcinomas by a mutation-specific antibody.

3576 Background: BRAF encodes a serine-threonine kinase that is a downstream effector of activated RAS. A point mutation (V600E) in BRAF occurs in a subset of colorectal cancers (CRCs) and is associated with adverse outcome and may predict non response to anti-EGFR antibodies. Detection of a BRAFV600E mutation in a CRC with microsatellite instability indicates a sporadic origin and excludes Lynch Syndrome. While BRAFV600E mutation status is determined using a DNA-based assay, antibodies against the BRAFV600E protein have recently been developed. We examined mutant BRAFV600E protein expression and its concordance with mutation status. Methods: Primary stage III colon carcinomas (50 BRAFV600E mutation carriers and 25 wild-type cases) were studied from a completed phase III adjuvant trial comparing FOLFOX +/- cetuximab (NCCTG N0147). In archival resection specimens, immunohistochemistry (IHC) was performed using a pan-BRAF antibody and a V600E mutation-specific antibody raised against an immunogenic syntheti...