title: External quality assessment for KRAS testing is needed: setup of a European program and report of the first joined regional quality assessment rounds.
abstract: The use of epidermal growth factor receptor-targeting antibodies in metastatic colorectal cancer has been restricted to patients with wild-type KRAS tumors by the European Medicines Agency since 2008, based on data showing a lack of efficacy and potential harm in patients with mutant KRAS tumors. In an effort to ensure optimal, uniform, and reliable community-based KRAS testing throughout Europe, a KRAS external quality assessment (EQA) scheme was set up. The first large assessment round included 59 laboratories from eight different European countries. For each country, one regional scheme organizer prepared and distributed the samples for the participants of their own country. The samples included unstained sections of 10 invasive colorectal carcinomas with known KRAS mutation status. The samples were centrally validated by one of two reference laboratories. The laboratories were allowed to use their own preferred method for histological evaluation, DNA isolation, and mutation analysis. In this study, we analyze the setup of the KRAS scheme. We analyzed the advantages and disadvantages of the regional scheme organization by analyzing the outcome of genotyping results, analysis of tumor percentage, and written reports. We conclude that only 70% of laboratories correctly identified the KRAS mutational status in all samples. Both the false-positive and false-negative results observed negatively affect patient care. Reports of the KRAS test results often lacked essential information. We aim to further expand this program to more laboratories to provide a robust estimate of the quality of KRAS testing in Europe, and provide the basis for remedial measures and harmonization.
authors: University of Leuven, Centre for Human Genetics, Research Unit Biomedical Quality Assurance Leuven, Herestraat 49, Box 602, 3000, Leuven, Belgium.
authors: Ellen
authors: E
authors: Bellon
authors: Marjolijn J L
authors: MJ
authors: Ligtenberg
authors: Sabine
authors: S
authors: Tejpar
authors: Karen
authors: K
authors: Cox
authors: Gert
authors: G
authors: de Hertogh
authors: Karin
authors: K
authors: de Stricker
authors: Anders
authors: A
authors: Edsjö
authors: Vassilis
authors: V
authors: Gorgoulis
authors: Gerald
authors: G
authors: Höfler
authors: Andreas
authors: A
authors: Jung
authors: Athanassios
authors: A
authors: Kotsinas
authors: Pierre
authors: P
authors: Laurent-Puig
authors: Fernando
authors: F
authors: López-Ríos
authors: Tine Plato
authors: TP
authors: Hansen
authors: Etienne
authors: E
authors: Rouleau
authors: Peter
authors: P
authors: Vandenberghe
authors: Johan J M
authors: JJ
authors: van Krieken
authors: Elisabeth
authors: E
authors: Dequeker
mesh_terms: D000906:Antibodies; D015179:Colorectal Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods / Q000592:standards*; D066246:ErbB Receptors / Q000276:immunology; D005060:Europe; D011905:Genes, ras; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007755:Laboratories, Hospital / Q000592:standards*; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D011785:Quality Assurance, Health Care; D011786:Quality Control; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000906:Antibodies; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins