K-RAS STATUS IN PRIMARY COLORECTAL TUMOURS CORRELATE WITH K-RAS STATUS IN RELATED METASTATIC SITES: IMPLICATIONS FOR TREATMENT WITH ANTI-EGFR ANTIBODIES IN CLINICAL SETTING

Background: Several studies demonstrated that K-Ras codon 12 and 13 mutations in tumor samples can predict resistance to cetuximab and panitunumab-based treatments in metastatic colorectal cancer patients. The aim of this study was to evaluate the grade of concordance of K-Ras status between primary and related metastatic samples. Material and methods: we retrospectively analysed K-Ras mutation from primary tumours and related metastatic sites in 107 colorectal cancer patients. 99 patients were available for our analysis. The site of primary tumour was colon in 79 patients (79.8%) and rectum in 20 patients (20.2%). Metastatic sites analyzed were liver in 80 patients (80.8%), lung in 7 patients (7.1%), other sites in 12 patients (12.1%). There were 50 men (50.5%); median age at diagnosis was 71 years (range, 41-84 to years). DNA was extracted from paraffin-embedded tumour. K-Ras point mutations in codons 12 and 13 were investigated according to standard procedures. Results: 8 patients were excluded from the analysis for the absence of tumour tissue in the analysed sample. K-Ras mutation was observed in 38 (38.4%) primary tumours and in 36 (36.4%) related metastatic sites. The grade of concordance between primary and metastatic sites was of 96.0% (95% CI: 90.0 to 98.9%). Discordance was observed in only 4 (4%) patients. In particular in 1 patient K-RAS was wild type in primary tumour and mutated in metastatic site; in 3 patients K-Ras was mutated in primary tumour and wild type in metastatic site. Conclusions: Our results clearly and definitively state that the detection of the K-Ras mutation in primary colorectal cancer is adequate for planning therapy with cetuximab and/or panitunumab in metastatic colorectal cancer patients because the grade of concordance between primary and related metastatic sites is near to 100%