Concordance in KRAS and BRAF mutations in endoscopic biopsy samples and resection specimens of colorectal adenocarcinoma
Abstract
Background KRAS testing is mandatory if anti-EGFR therapy is considered in patients with metastatic colorectal cancer (CRC). In addition, BRAF mutations seem to be an important negative prognostic factor. The aim of this study is to establish the concordance of KRAS and BRAF mutational status in paired biopsy and resection specimens of primary CRC using several analytic methods.Methods DNA was extracted from paraffin blocks of 126 CRC patients. KRAS codon 12/13 and BRAF V600E mutational status was assessed using high resolution melting (HRM), direct sequencing (DS) of the HRM polymerase chain reaction (PCR) product. In addition, the Therascreen Amplification Refractory Mutation System (ARMS)-Scorpion KRAS assay and BRAF pyrosequencing were employed; both assays claim to require less tumour cells in comparison with DS.Results KRAS and BRAF were found to be mutually exclusive. Mutation frequencies were 33.9% for KRAS, and for BRAF 19.0%, respectively. Concordance of KRAS mutational status between biopsy and resection specimens was 97.4% (ARMS), 98.4% (DS) and 99.2% (HRM), respectively. For BRAF concordance was 98.4% (Pyro, DS) and 99.2% (HRM).Conclusions KRAS and BRAF mutational status of endoscopic biopsies and resection specimens of CRC showed a >95% concordance. Endoscopic biopsies can be confidently used for molecular analysis.
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The sensitivity of RAS mutation testing methods ranges from 10 to 25% for direct sequencing (least sensitive) to less than 1% for BEAMing (most sensitive), with other methods generally having sensitivities of 1-10%.
“The sensitivity of these methods ranged from 10 to 25% for direct sequencing (the least sensitive) to less than 1% for BEAMing (the most sensitive), with other methods generally having sensitivities of 1–10% [49,50]”
From The Role of KRAS Mutations in Colorectal Cancer: Biological Insights, Clinical Implications, and Future Therapeutic Perspectives (2025) · cites this paper as [50]
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Takeda, M., Yoshida, S., Inoue, T., Sekido, Y., Hata, T., Hamabe, A., Ogino, T., Miyoshi, N., Uemura, M., Yamamoto, H., et al. (2025) · Cancers · doi:10.3390/cancers17030428 · Cited by 82 · see citing works
- Authors
- Krol, L. C., ’t Hart, N. A., Methorst, N., Knol, A. J., Prinsen, C., & Boers, J. E.
- Affiliations
- Isala (NL)
- Corresponding author
- Boers, J.E.
- ORCID
- Boers, J.E.
- Venue
- European Journal of Cancer
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 48
- Issue
- 7
- Pages
- 1108-1115
- ISSN
- 0959-8049 (ISSN-L)
- OpenAlex
- W2160668006
- Cited by
- 31
- References
- 36
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 4 · 2014: 7 · 2013: 5 · 2012: 2
- FWCI
- 2.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- 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, BRAF V600E mutation, colorectal adenocarcinoma, endoscopic biopsy, surgical resection specimens, concordance, anti-EGFR therapy, high-resolution melting analysis, pyrosequencing, allele-specific PCR
- MeSH terms
- Adenocarcinoma, Aged, Biopsy, Endoscopy, Female, Humans, Male, Mutation, Genes, ras, Colorectal Neoplasms, Proto-Oncogene Proteins B-raf
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