The Prognostic Utilities of DNA Mismatch Repair Status and KRAS and BRAF Mutation in Korean Colorectal Cancer Patients: The KASID Multicenter Study

Abstract

Introduction: KRAS, BRAF, and DNA mismatch repair (MMR) mutations aid clinical decision-making for colorectal cancer (CRC) patients. To ensure accurate predictions, the prognostic utilities of these biomarkers and their combinations must be individualized for patients with various TNM stages. Methods: Here, we retrospectively analyzed the clinicopathological features of 904 Korean CRC patients who underwent CRC surgery in three teaching hospitals from 2011 to 2013; we also assessed the prognostic utilities of KRAS, BRAF, and MMR mutations in these patients. Results: The overall frequencies of KRAS and BRAF mutations were 35.8% and 3.2%, respectively. Sixty-nine patients (7.6%) lacking expression of ≥1 MMR protein were considered MMR protein deficient (MMR-D); the remaining patients were considered MMR protein intact. KRAS mutations constituted an independent risk factor for shorter overall survival (OS) in TNM stage I-IV and stage III patients. BRAF mutations were associated with shorter OS in TNM stage I-IV patients. MMR-D status was strongly positive prognostic in TNM stage I-II patients. Discussion/Conclusion: To our knowledge, this is the first multicenter study to explore the prognostic utilities of KRAS, BRAF, and MMR statuses in Korean CRC patients. Various combinations of KRAS, BRAF, and DNA MMR mutations serve as genetic signatures that affect tumor behavior; they are prognostic in CRC patients.