Prognostic Impact of Deficient DNA Mismatch Repair and Mutations inKRAS, andBRAFV600Ein 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 ofMLH1in tumors that often carry mutations in oncogenicBRAFV600E. ActivatingBRAFV600EandKRASmutations 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.
Mayo Clinic and Mayo Cancer Center, Rochester, Minnesota, United States of America, 200 First St SW, Rochester, MN 55905. Telephone: 507-255-5713.
Aziz
A
Zaanan
Departement of Hepato-Gastro-Enterology, Hôpital La Pitié Salpetrière, Université Paris VI, 47-83 boulevard de l'Hôpital, 75651 Paris Cedex 13, France. Telephone: 33 1 42 16 10 45.
Jean-Baptiste
JB
Bachet
Department of Medical Oncology, Hôpital Saint-Antoine, Université Paris VI, 184 rue du Faubourg Saint-Antoine, 75571 Paris Cedex 12, France. Telephone: 33 1 71 97 04 01.
Thierry
T
André
Mayo Clinic and Mayo Cancer Center, Rochester, Minnesota, United States of America, 200 First St SW, Rochester, MN 55905. Telephone: 507-255-5713.
Frank A
FA
Sinicrope
5-fluorouracil; Adjuvant Chemotherapy; BRAF; Biomarker; Colorectal cancer; DNA Mismatch repair; KRAS; Microsatellite instability; Predictive; Prognosis; oxaliplatin