ArticleVirchows Archiv : an international journal of pathology2013
KRAS mutation analysis on low percentage of colon cancer cells: the importance of quality assurance.
Article in Virchows Archiv : an international journal of pathology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 29 citations in OpenAlex.
- Conventional and semi-automatic histopathological analysis of tumor cell content for multigene sequencing of lung adenocarcinoma.Translational lung cancer research · 2021Article
- Mutational Screening of BRCA1/2 Genes as a Predictive Factor for Therapeutic Response in Epithelial Ovarian Cancer: A Consensus Guide from the Spanish Society of Pathology (SEAP-IAP) and the Spanish Society of Human Genetics (AEGH).Virchows Archiv : an international journal of pathology · 2020Review
- RAS testing for colorectal cancer patients is reliable in European laboratories that pass external quality assessment.Virchows Archiv : an international journal of pathology · 2018Article
- Testing forDisease markers · 2018Article
- Current companion diagnostics in advanced colorectal cancer; getting a bigger and better piece of the pie.Journal of gastrointestinal oncology · 2017Review
- Adequately defining tumor cell proportion in tissue samples for molecular testing improves interobserver reproducibility of its assessment.Virchows Archiv : an international journal of pathology · 2017Article
- Detection of KRAS, NRAS and BRAF by mass spectrometry - a sensitive, reliable, fast and cost-effective technique.Diagnostic pathology · 2015Article
- RAS testing in metastatic colorectal cancer: excellent reproducibility amongst 17 Dutch pathology centers.Oncotarget · 2015Article
- Guidance for laboratories performing molecular pathology for cancer patients.Journal of clinical pathology · 2014Review
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Authors and funding
18 authors at 11 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
KRAS mutation testing is mandatory for patients with metastatic colorectal cancer who are eligible for treatment with an epidermal growth factor receptor targeting agent, since tumors with a mutation are not sensitive to the drug. Several methods for mutation testing are in use and the need for external quality assurance has been demonstrated. An often little addressed but important issue in external quality assurance schemes is a low percentage of tumor cells in the test samples, where the analytical sensitivity of most tests becomes critical. Using artificial samples based on a mixture of cell lines with known mutation status of the KRAS gene, we assessed the reliability of a series of commonly used methods (Sanger sequencing, high resolution melting, pyrosequencing, and amplification refractory mutation system-polymerase chain reaction) on samples with 0, 2.5, 5, 10, and 15 % mutated cells. Nine laboratories throughout Europe participated and submitted a total of ten data sets. The limit of detection of each method differed, ranging from >15-5 % tumor cells. All methods showed a decreasing correct mutation call rate proportionally with decreasing percentage of tumor cells. Our findings indicate that laboratories and clinicians need to be aware of the decrease in correct mutation call rate proportionally with decreasing percentage of tumor cells and that external quality assurance schemes need to address the issue of low tumor cell percentage in the test samples.
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