Impact of Specific KRAS Mutation in Exon 2 on Clinical Outcome of Chemotherapy- and Radiotherapy-Treated Colorectal Adenocarcinoma Patients

Abstract

Background and Objectives: Knowledge obtained via high-throughput technologies, used for tumor genome sequencing or identifying gene expression and methylation signatures, is clinically applicable thanks to molecular characterization in the context of tumor development and progression. This study was conducted to assess the impact of specific KRAS mutation in codons 12 and 13 on clinical outcome of chemotherapy and radiotherapy in colorectal cancer patients. Methods: A total of 239 samples of colorectal adenocarcinoma underwent histological evaluation and DNA isolation. Results and Conclusions: Patients with a mutation in KRAS codon 13 experienced worse outcome than those with a mutation in KRAS codon 12. Moreover, the cases of mutations in KRAS codons 12 or 13 were associated with a significantly higher mortality than the cases of wild-type KRAS, and some patients with KRAS mutated in codon 12 had an exceptionally long overall survival. Finally, primary preoperative radiation therapy followed by surgery significantly increased overall survival more efficiently than surgery followed by chemotherapy. This should be investigated in further studies. The fact that all patients treated with radiotherapy + surgery were alive, again focused our attention on the effect of preoperative radiation therapy on the prognosis for colorectal cancer patients. However, the number of patients in this subgroup is too small to allow any specific explanation for this observation. We should, rather, point out a problem for further investigation.