Disease progression and overall survival in Sardinian patients with colorectal cancer according to the kras mutational status

Background: Mutation in KRAS gene has been extensively demonstrated to act as a predictor of response to EGFR-targeted agents in patients with colorectal cancer. Less is known about the significance of KRAS mutation as a prognostic factor of disease progression and survival, independently of anti-EGFR therapy. The aim of the present study is to evaluate the prognostic role of the KRAS mutational status in a cohort of Sardinian patients with colorectal cancer. Materials and methods: Five hundred and fifty-one consecutive Sardinian patients with histologically proven diagnosis of invasive colorectal carcinoma were included into the study, regardless of age at diagnosis and disease characteristics. Clinical and pathological disease features were confirmed by medical records, pathology reports, and cancer registry data. For mutational analysis, paraffin embedded tissue samples with at least 70% neoplastic cells were processed; genomic DNA was isolated from tissue sections and DNA quality assessed for each specimen. The coding sequences and splice junctions of exons 2, 3, and 4 in KRAS gene were screened for mutations by direct automated sequencing. Results: KRAS mutations were detected in 183/551 (33%) patients; three of them presented the coexistence of two KRAS mutations in the same primary tumor tissue. Among the 186 KRAS mutations identified, two thirds (125; 67%) were located in codon 12, about one fifth (36; 19.4%) in codon 13, and about one tenth (18; 9.7%) in codon 61. The remaining mutations (7; 3.8%) were detected in uncommonly-affected codons of the KRAS gene. No significant correlations between KRAS mutations and sex, age at diagnosis, anatomical location, and disease stage at the time of diagnosis were found. No prognostic values of KRAS mutations were found for either the time to progression as metastatic disease or the overall survival. When patients were stratified by both KRAS mutational status and sex, a significantly better metastasis-free survival was observed for KRAS-mutated male cases. Considering the gene positions of the identified KRAS mutations, no correlation with both the time to progression as metastatic disease and overall survival was observed. Conclusions: Our data suggest that KRAS mutations are correlated to a slower progression of the disease in males with colorectal cancer from Sardinia, irrespectively of the diagnosis age and the mutation position. Such findings were not confirmed considering the overall survival in both sexes.