KRAS mutation analysis: A comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients

Knijn, N; Mekenkamp, L J M; Klomp, M; Vink-Börger, M E; Tol, J; Teerenstra, S; Meijer, J W R; Tebar, M; Riemersma, S; van Krieken, J H J M; Punt, C J A; Nagtegaal, I D

doi:10.1038/bjc.2011.26

Cited by 291Colorectal Cancer Treatments and StudiesGenetic factors in colorectal cancerColorectal Cancer Surgical Treatments

KRAS mutation analysis: A comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients

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Knijn, N, Mekenkamp, L J M, Klomp, M, Vink-Börger, M E, Tol, J, Teerenstra, S, Meijer, J W R, Tebar, M +4 more·2011·British Journal of Cancer

DOI 10.1038/bjc.2011.26PMC PMC3065268

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Abstract

BACKGROUND: KRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor antibody in metastatic colorectal cancer (CRC). KRAS mutation analysis is usually performed on primary tumour tissue because metastatic tissue is often not available. However, controversial data are available on the concordance of test results between primary tumours and corresponding metastases. We assessed the concordance of KRAS mutation status in a study of 305 primary colorectal tumours and their corresponding liver metastases. METHODS: Patients with histologically confirmed CRC who underwent surgical resection of the primary tumour and biopsy or surgical resection of the corresponding liver metastasis were included. KRAS mutation analysis was performed for codons 12 and 13. RESULTS: KRAS mutation was detected in 108 out of 305 primary tumours (35.4%). In 11 cases (3.6%), we found a discordance between primary tumour and metastasis: 5 primary tumours had a KRAS mutation with a wild-type metastasis, 1 primary tumour was wild type with a KRAS mutation in the metastasis, and in 5 cases the primary tumour and the metastasis had a different KRAS mutation. CONCLUSION: We observed a high concordance of KRAS mutation status of 96.4% (95% CI 93.6-98.2%) between primary colorectal tumours and their corresponding liver metastases. In only six patients (2.0%; 95% CI 0.7-4.2%), the discordance was clinically relevant. In this largest and most homogenous study to date, we conclude that both primary tumours and liver metastases can be used for KRAS mutation analysis.

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Discordance in KRAS mutation status is rare in distant organ metastases (less than 10%).
“discordance in KRAS mutation status is rare in distant organ metastases (less than 10%) [52,53]”
From The Role of KRAS Mutations in Colorectal Cancer: Biological Insights, Clinical Implications, and Future Therapeutic Perspectives (2025) · cites this paper as [53]

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Mutation analysis of KRAS in primary colorectal cancer and matched metastases by means of highly sensitivity molecular assay
Miglio, U., Mezzapelle, R., Paganotti, A., Allegrini, S., Veggiani, C., Antona, J., Gentilli, S., Monga, G., Alabiso, O., & Boldorini, R. L. (2013) · Pathology - Research and Practice · doi:10.1016/j.prp.2013.02.006 · Cited by 26 · see citing works

Authors: Knijn, N., Mekenkamp, L. J. M., Klomp, M., Vink-Börger, M. E., Tol, J., Teerenstra, S., Meijer, J. W. R., Tebar, M., Riemersma, S., van Krieken, J. H. J. M., Punt, C. J. A., & Nagtegaal, I. D.
Affiliations: Radboud University Medical Center (NL)
Rijnstate Hospital (NL)
Corresponding author: Nagtegaal, I D
ORCID: Knijn, N
Tol, J
Teerenstra, S
Riemersma, S
Punt, C J A
Nagtegaal, I D
Venue: British Journal of Cancer
Publisher: Springer Science and Business Media LLC
Published: 2011-03
Volume: 104
Issue: 6
Pages: 1020-1026
ISSN: 0007-0920 (ISSN-L)
1532-1827
DOI: 10.1038/bjc.2011.26
PMC: PMC3065268
OpenAlex: W2011288277
Cited by: 291
References: 34
Citations by year: 2026: 5 · 2025: 7 · 2024: 5 · 2023: 11 · 2022: 8 · 2021: 15 · 2020: 21 · 2019: 20 · 2018: 20 · 2017: 30 · 2016: 31 · 2015: 24 · 2014: 33 · 2013: 21 · 2012: 34
FWCI: 14.78
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
www.springer.com/tdm (unspecified)
Locations: British Journal of Cancer (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Pure Amsterdam UMC (submittedVersion)
Radboud Repository (Radboud University) (submittedVersion)
Radboud Repository (Radboud University) (submittedVersion, other-oa)
Funders: Dutch Colorectal Cancer Group
Topics: Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
Keywords: KRAS mutation, colorectal cancer, liver metastasis, primary tumor, codon 12 and 13 mutations, anti-EGFR antibody therapy, predictive biomarkers
MeSH terms: Aged, Carcinoma, DNA Mutational Analysis, Female, Humans, Liver Neoplasms, Male, Middle Aged, Models, Biological, Mutation, Genes, ras, Colorectal Neoplasms, Cohort Studies, Multicenter Studies as Topic, Matched-Pair Analysis

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KRAS mutation analysis: A comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients

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