title: External quality assessment unravels interlaboratory differences in quality of RAS testing for anti-EGFR therapy in colorectal cancer.
abstract: BACKGROUND
  Regulations for the selection of patients with metastatic colorectal cancer for anti-EGFR treatment changed at the end of 2013. The set of mutations to be tested extended from KRAS codons 12 and 13 to KRAS and NRAS exons 2, 3, and 4. A European external quality assessment scheme monitored the performance of laboratories and evaluated the implementation of the new regulations.
  
  
  METHODS
  The 131 participating laboratories received 10 samples of formalin-fixed paraffin-embedded material, including RAS (exon 2, 3, 4) and BRAF mutations. Mock clinical data were provided for three cases. Using their routine methods, laboratories determined the genotypes and submitted three written reports. Assessors scored the results according to predefined evaluation criteria.
  
  
  RESULTS
  Half of the participants (49.3%) had completely implemented the new test requirements (codons 12, 13, 59, 61, 117, and 146 of KRAS and NRAS), and 96 laboratories (73.3%) made no genotype mistakes. Correct nomenclature, according to the Human Genome Variation Society, was used by 82 laboratories (62.6%).
  
  
  CONCLUSIONS
  Although regulations were effective for several months, many laboratories were not ready for full RAS testing in the context of anti-EGFR therapy. Nevertheless, in each participating country, there are laboratories that provide complete and correct testing. External quality assessments can be used to monitor implementation of new test regulations and to stimulate the laboratories to improve their testing procedures. Because the results of this program are available on the website of the European Society of Pathology, patients and clinicians can refer test samples to a reliable laboratory.
authors: Biomedical Quality Assurance Research Unit, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium; Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands; Cell Biology and Biotherapy Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - IRCCS, Naples, Italy; Department of Pathology, UZ Leuven, Leuven, Belgium.
authors: Véronique
authors: V
authors: Tack
authors: Biomedical Quality Assurance Research Unit, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium; Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands; Cell Biology and Biotherapy Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - IRCCS, Naples, Italy; Department of Pathology, UZ Leuven, Leuven, Belgium.
authors: Marjolijn J L
authors: MJ
authors: Ligtenberg
authors: Biomedical Quality Assurance Research Unit, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium; Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands; Cell Biology and Biotherapy Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - IRCCS, Naples, Italy; Department of Pathology, UZ Leuven, Leuven, Belgium.
authors: Lien
authors: L
authors: Tembuyser
authors: Biomedical Quality Assurance Research Unit, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium; Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands; Cell Biology and Biotherapy Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - IRCCS, Naples, Italy; Department of Pathology, UZ Leuven, Leuven, Belgium.
authors: Nicola
authors: N
authors: Normanno
authors: Biomedical Quality Assurance Research Unit, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium; Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands; Cell Biology and Biotherapy Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - IRCCS, Naples, Italy; Department of Pathology, UZ Leuven, Leuven, Belgium.
authors: Sara
authors: S
authors: Vander Borght
authors: Biomedical Quality Assurance Research Unit, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium; Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands; Cell Biology and Biotherapy Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - IRCCS, Naples, Italy; Department of Pathology, UZ Leuven, Leuven, Belgium.
authors: J
authors: J
authors: Han van Krieken
authors: Biomedical Quality Assurance Research Unit, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium; Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands; Cell Biology and Biotherapy Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - IRCCS, Naples, Italy; Department of Pathology, UZ Leuven, Leuven, Belgium els.dequeker@med.kuleuven.be.
authors: Elisabeth M C
authors: EM
authors: Dequeker
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D003062:Codon; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005091:Exons; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods*; D006801:Humans; D007755:Laboratories, Hospital / Q000592:standards*; D059021:Laboratory Proficiency Testing; D018579:Patient Selection; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D011785:Quality Assurance, Health Care; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D003062:Codon; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: Biological markers; Colorectal neoplasms; Patient safety; Quality assurance
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