Phenotypic differences among RAS mutational variations in colorectal cancer (CRC): Analysis of 1,001 patients in single institute.

Abstract

649 Background: RAS mutation has been reported as a predictor of benefit from anti EGFR therapies in the recent sub-analysis of some large prospective trials, PRIME, FIRE-3 and so on. On the other hand, some in vitro experiments had identified the differences of capability of GTP bounding and colony formation according to KRAS mutational variations. It remains unknown whether there are phenotypic differences clinically among RAS mutational variations as potentially negative predictive factors for anti EGFR treatments. This study aimed to reveal the prevalence and the phenotypic differences of these variations in a large cohort. Methods: Consecutive patients of 1,001 CRC from January 2012 to October 2013 were analyzed in this study. Multiplex genotyping of EGFR pathway was performed on archival samples using Luminex Assay (MABGEN and GENOSEARCH Mu-PACK, MBL) for KRAS including codons 61,146 and NRAS. We examined the correlation among mutation variations; KRAS G12D, G12V, G13D and other exon2, exon 3 and 4 and NRAS, and clinical phenotypic features. Statistical analysis was conducted by chi-square test. Results: The incidence of mutations; KRAS G12D, G12V, G13D, other exon2, exon 3 and 4, and NRAS were 16.2%, 10.0%, 6.4%, 7.0%, 4.6% and 3.5%, respectively. So called all RAS mutations were occupied in 47% in this cohort. There was no significant difference of prevalence among mutational variations according to clinical feature as follows; clinical stage, gender, age. In histopathology, moderately differentiated type of G12D was more frequent compared with other type of mutations. The respective proportion of KRAS exon 3 and 4, and NRAS mutations for left sided primary was relatively higher than those for right sided, although the frequency of other mutations were higher in right side. Conclusions: According to our analysis there were not so large phenotypic differences among these RAS mutational variations except histology and localization of primary. Futher follow up of this cohort will provide more information about treatment outcomes in near future.