Prognostic Value of KRAS Mutations in Codons 12 and 13 in South Egyptian Colorectal Cancer Patients

Abstract

Aims: The aim of the study was to assess the frequency of Kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutation, perform clinicopathologic characterization of KRAS mutated colorectal cancer (CRC), evaluation of the prognostic significance of KRAS mutations and their influences on the outcome in patients with CRC after curative surgical resection. Patients and Methods: This study included 79 previously untreated CRC cases presented to South Egypt Cancer Institute from January 2011 to June 2013.  Tumor samples were prospectively analyzed for KRAS mutations detection using DNA Clamp technique. Results: Genotyping revealed an overall mutation frequency of 31.6% in KRAS gene. 68% of the mutations were in codon 12 and 23% in codon 13. Patients with KRAS mutated CRC had statistically significant increase in the rate of local recurrence (P=.002) and distant metastases (P=.024) compared to patients with KRAS wild type CRC.  There was statistically significant poorer 2-year disease free survival (DFS) (61.6% vs 86.2%, P=.01) and overall survival (OS) (83.1% vs 90.7%, P=0.04) in cases with KRAS mutated vs KRAS wild type CRC. Codon 13 was associated with statistically significant lower 2-year DFS (46.9% vs 81.4%, P=.008) and OS (62.5% vs 91.4%, P=.009) compared to cases without codon 13 KRAS mutation. Conclusion: The prognostic significance of KRAS mutation status regarding survival and treatment outcome in CRC might form the basis for more specific adjuvant therapy to improve survival.