P-203 - KRAS mutational variations and characteristics in colorectal cancer(CRC): Analysis of over 1600 patients in single institute

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Biomarkers
Colon Cancer
Rectal Cancer
Presenter E. Shinozaki
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors E. Shinozaki1, Y. Miki2, M. Ueno3, M. Igarashi4, I. Nakayama4, H. Osumi1, M. Suenaga1, K. Chin1, M. Ogura5, M. Ozaka1, S. Matsusaka1, D. Takahari4, I. Takashi4, T. Wakatsuki6, T. Yamaguchi7, N. Mizunuma1
  • 1Cancer Institute Hospital of JFCR, Koto-ku/JP
  • 2Cancer Institute, Koto-ku/JP
  • 3Japanese Foundation for Cancer Research, Koto-ku/JP
  • 4Cancer Institute Hospital, Koto-ku/JP
  • 5Cancer Institute Hospital of Japanese Foundation for Cancer Research, Koto-ku/JP
  • 6Cancer Institute Hospital Department of gastroenterology, Koto-ku/JP
  • 7Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo/JP

Abstract

Introduction

KRAS mutations are known as a predictor of no benefit from anti EGFR therapies in CRC. And we used to test KRAS status in practice until now. KRAS exon 2 mutations which occupies 80% of all RAS mutations even consist of multiple genotypic variations. Some in vitro experiments had identified the differences on capability of GTP bounding and colony formation according to the KRAS mutational variations. It remains unknown whether there are phenotypic differences clinically among KRAS mutational variations as potentially negative predictive factors for anti EGFR treatments. This study aimed to summarize the prevalence and the phenotypic differences of these variations in KRAS in transition of RAS era.

Methods

Consecutive patients of 1615 CRC from 2010 to 2013 were analyzed in this study. Multiplex genotyping of KRAS mutation was performed using Luminex Assay. Furthermore archival samples testing between Jan 2012 to Oct 2013 were added to genotyping for KRAS including codons 61,146, NRAS, PIK3CA, BRAF (MABGEN, GENOSEARCH Mu-PACK, MBL). We examined the correlation among mutation variations; KRAS exon2, partly, 3 and 4, NRAS, PIK3CA, BRAF and clinical phenotypic features. Statistical analysis was conducted by Fisher's exact probability test. Multivariate stepwise logistic regression analysis was performed about variables based on the results of univariate analysis and mutation status.

Results

KRAS mutations were occupied in 36.5% in this cohort (n = 1615). The incidence of mutations; KRAS G12D, G12V, G13D and other exon2 were 14.9%, 9.7%, 6.4% and 6.6%, respectively (including co-mutation). In univariate analysis there was some imbalance of clinical features among mutational variations as follows; gender, histopathology and location of primary tumor site. In the samples testing between Jan 2012 to Oct 2013 (n = 1001); KRAS codon12 and 13, codon61 and 146, BRAF, NRAS and PIK3CA were 38%, 4.6%, 5.1%, 3.5% and 9.1%, respectively. 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 those of other mutations were higher in right side.

Conclusion

According to our analysis there were some phenotypic differences among these KRAS mutational variations. Further follow up of this cohort will provide more information about treatment outcomes in near future. We will attempt to add the data of 2014 to this analysis at the presentation.