Can Serum be Used for Analyzing the KRAS Mutation Status in Patients with Advanced Colorectal Cancer?

KRAS mutations have been used widely as prognostic or predictive marker in patients with advanced colorectal cancer (CRC). However, it may be difficult to obtain a tumor tissue for analyzing the status of KRAS mutation in large proportion of patients with advanced disease.

We obtained pairs of tumor and serum samples from 65 patients with advanced CRC, between March 2008 and July 2011. KRAS mutation status from the tumor samples was analyzed by genomic polymerase chain reaction and direct sequence, and KRAS mutation status from the serum samples was determined by a genomic polymerase chain reaction-restriction fragment length polymorphism assay.

KRAS mutations were detected in the serum samples of 26 patients and in the tumor samples of 31 patients. KRAS mutation status in the serum and tumor samples was consistent in 44 of the 65 pairs (67.7%). There was a significant correlation between the mutations detected in the serum sample and the mutations detected in the matched tumor sample (correlation index, 0.35; p < 0.004). Twenty-two of the 57 patients (38.5%) received anti-epidermal growth factor receptor therapy as any line therapy. There was no significant difference in the overall survival (OS) in accordance to the status of KRAS mutations in both the serum and tumor samples (p > 0.05). In a multivariate analysis, liver metastasis and no cytoreductive operation were independent prognostic factors for decreased OS.

The serum sample might alternatively be used when it is difficult to obtain tumor tissues for analyzing the status of KRAS mutation in patients with advanced CRC.