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

Abstract

<b><i>Introduction:</i></b> <i>KRAS</i>, <i>BRAF</i>, 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. <b><i>Methods:</i></b> 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 <i>KRAS</i>, <i>BRAF</i>, and MMR mutations in these patients. <b><i>Results:</i></b> The overall frequencies of <i>KRAS</i> and <i>BRAF</i> 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. <i>KRAS</i> mutations constituted an independent risk factor for shorter overall survival (OS) in TNM stage I–IV and stage III patients. <i>BRAF</i> 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. <b><i>Discussion/Conclusion:</i></b> To our knowledge, this is the first multicenter study to explore the prognostic utilities of <i>KRAS</i>, <i>BRAF</i>, and MMR statuses in Korean CRC patients. Various combinations of <i>KRAS</i>, <i>BRAF</i>, and DNA MMR mutations serve as genetic signatures that affect tumor behavior; they are prognostic in CRC patients.