title: Higher quality of molecular testing, an unfulfilled priority: Results from external quality assessment for KRAS mutation testing in colorectal cancer.
abstract: Precision medicine is now a key element in clinical oncology. RAS mutational status is a crucial predictor of responsiveness to anti-epidermal growth factor receptor agents in metastatic colorectal cancer. In an effort to guarantee high-quality testing services in molecular pathology, the European Society of Pathology has been organizing an annual KRAS external quality assessment program since 2009. In 2012, 10 formalin-fixed, paraffin-embedded samples, of which 8 from invasive metastatic colorectal cancer tissue and 2 artificial samples of cell line material, were sent to more than 100 laboratories from 26 countries with a request for routine KRAS testing. Both genotyping and clinical reports were assessed independently. Twenty-seven percent of the participants genotyped at least 1 of 10 samples incorrectly. In total, less than 5% of the distributed specimens were genotyped incorrectly. Genotyping errors consisted of false negatives, false positives, and incorrectly genotyped mutations. Twenty percent of the laboratories reported a technical error for one or more samples. A review of the written reports showed that several essential elements were missing, most notably a clinical interpretation of the test result, the method sensitivity, and the use of a reference sequence. External quality assessment serves as a valuable educational tool in assessing and improving molecular testing quality and is an important asset for monitoring quality assurance upon incorporation of new biomarkers in diagnostic services.
authors.affiliation: Biomedical Quality Assurance Research Unit, Department of Public Health and Primary Care, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Lien
authors.initials: L
authors.lastname: Tembuyser
authors.affiliation: Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Marjolijn J L
authors.initials: MJ
authors.lastname: Ligtenberg
authors.affiliation: Cell Biology and Biotherapy Unit, National Institute for the Study and Treatment of Cancer "Fondazione Giovanni Pascale" - IRCCS, Naples, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Normanno
authors.affiliation: Biomedical Quality Assurance Research Unit, Department of Public Health and Primary Care, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Delen
authors.affiliation: Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: J Han
authors.initials: JH
authors.lastname: van Krieken
authors.affiliation: Biomedical Quality Assurance Research Unit, Department of Public Health and Primary Care, KU Leuven-University of Leuven, Leuven, Belgium. Electronic address: els.dequeker@med.kuleuven.be.
authors.forename: Elisabeth M C
authors.initials: EM
authors.lastname: Dequeker
mesh_terms: D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods; D006801:Humans; D059021:Laboratory Proficiency Testing / Q000379:methods; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012007:Rectum / Q000378:metabolism / Q000473:pathology; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins