Prognostic role of KRAS mutations in Sardinian patients with colorectal carcinoma

Mutation of KRAS gene is a predictor of a poor clinical response to EGFR-targeted agents in patients affected by colorectal cancer (CRC), but its significance as a global prognostic factor is not clear. The aim of this study is to evaluate the impact of the KRAS mutational status on time to first metastasis (TTM) and overall survival (OS) in a cohort of Sardinian CRC patients. Five hundred and fifty-one patients with metastatic CRC at the time of enrolment were included. Clinical and pathological features of the disease, including follow-up information, were obtained by medical records and cancer registry data. For mutational analysis formalin-fixed paraffin-embedded tissue samples were processed using a standard protocol. The coding sequence and splice junctions of exons 2 and 3 in KRAS gene were screened for mutations by direct automated sequencing. Overall, 186 KRAS mutations were detected in 183/551 (33%) patients: 125 (67%) were located in codon 12, 36 (19%) in codon 13, and 18 (10%) in codon 61. The remaining mutations (7; 4%) were detected in uncommonly-affected codons. No significant correlation between KRAS mutations and sex, age, anatomical location, and stage of the disease at the time of diagnosis was found. Furthermore, no prognostic value of KRAS mutations was found considering either TTM or OS. When patients were stratified by both KRAS mutational status and sex, males were significantly associated with a longer time to the onset of first metastasis. Our data suggest that KRAS mutation is correlated to a slower metastatic progression in males with colorectal cancer from Sardinia, irrespectively of the age at diagnosis and the codon of the mutation