Open Access Short Report

Reliability of KRAS mutation testing in metastatic colorectal cancer patients across five laboratories

Heather Spencer Feigelson1*, Katrina AB Goddard2, Monique A Johnson3, Kellyan C Funk1, Alanna Kulchak Rahm1, Tia L Kauffman2, Dhananjay A Chitale4, Loic Le Marchand5 and C Sue Richards3

Author Affiliations

1 Institute for Health Research Legacy Highlands, Kaiser Permanente Colorado, Suite 300, P.O. Box 378066, Denver, CO, 80237-8066, USA

2 Kaiser Permanente Northwest, Center for Health Research, 3800 N. Interstate Avenue, Portland, OR, 97227, USA

3 Molecular and Medical Genetics, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR, 97239-3098, USA

4 Department of Pathology and Laboratory Medicine, Henry Ford Hospital, 2799 W. Grand Blvd., Detroit, MI, 48202, USA

5 University of Hawaii Cancer Center, 677 Ala Moana Boulevard, Suite 901, Honolulu, HI, 96813, USA

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BMC Research Notes 2012, 5:196  doi:10.1186/1756-0500-5-196

Published: 25 April 2012



Mutations in the KRAS gene are associated with poor response to epidermal growth factor receptor inhibitors used in the treatment of metastatic colorectal cancer. Factors influencing KRAS test results in tumor specimens include: tumor heterogeneity, sample handling, slide preparation, techniques for tumor enrichment, DNA preparation, assay design and sensitivity. We evaluated comparability and consistency of KRAS test results among five laboratories currently being used to determine KRAS mutation status of metastatic colorectal cancer specimens in a large, multi-center observational study.


Twenty formalin-fixed paraffin-embedded human colorectal cancer samples from colon resections previously tested for KRAS mutations were selected based on mutation status (6 wild type, 8 codon 12 mutations, and 6 codon 13 mutations). We found good agreement across laboratories despite differences in mutation detection methods. Eighteen of twenty samples (90%) were concordant across all five labs. Discordant results are likely not due to laboratory error, but instead to tumor heterogeneity, contamination of the tumor sample with normal tissue, or analytic factors affecting assay sensitivity.


Our results indicate commercial and academic laboratories provide reliable results for the common KRAS gene mutations at codons 12 and 13 when an adequate percentage of tumor cells is present in the sample.

KRAS; Colorectal cancer; EGFR; Laboratory error