Prognostic Impact of Deficient DNA Mismatch Repair and Mutations in KRAS, and BRAFV600E in Patients with Lymph Node-Positive Colon Cancer.

While tumor stage remains the key determinant of colorectal cancer (CRC) prognosis and treatment, there is considerable stage-independent variability in clinical outcome. Molecular markers hold promise for explaining variations in clinical behavior, and may identify patient subsets with differential efficacy and survival after adjuvant chemotherapy which is standard of care for patients with lymph node-positive, i.e., stage III, colon cancer. An increased understanding of the molecular evolution and progression of CRC has identified two major pathways of tumorigenesis that are characterized by chromosomal instability or microsatellite instability (MSI). MSI is a consequence of deficient DNA mismatch repair (MMR) that is generally due to epigenetic inactivation of MLH1 in tumors that often carry mutations in oncogenic BRAFV600E . Activating BRAFV600E and KRAS mutations are mutually exclusive and in this article, we review the current status of these mutations and MMR status as prognostic biomarkers in stage III colon cancers.