title: Assessing standardization of molecular testing for non-small-cell lung cancer: results of a worldwide external quality assessment (EQA) scheme for EGFR mutation testing.
abstract: BACKGROUND
  The external quality assurance (EQA) process aims at establishing laboratory performance levels. Leading European groups in the fields of EQA, Pathology, and Medical and Thoracic Oncology collaborated in a pilot EQA scheme for somatic epidermal growth factor receptor (EGFR) gene mutational analysis in non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  EQA samples generated from cell lines mimicking clinical samples were provided to participating laboratories, each with a mock clinical case. Participating laboratories performed the analysis using their usual method(s). Anonymous results were assessed and made available to all participants. Two subsequent EQA rounds followed the pilot scheme.
  
  
  RESULTS
  One hundred and seventeen labs from 30 countries registered and 91 returned results. Sanger sequencing and a commercial kit were the main methodologies used. The standard of genotyping was suboptimal, with a significant number of genotyping errors made. Only 72 out of 91 (72%) participants passed the EQA. False-negative and -positive results were the main sources of error. The quality of reports submitted was acceptable; most were clear, concise and easy to read. However, some participants reported the genotyping result in the absence of any interpretation and many obscured the interpretation required for clinical care.
  
  
  CONCLUSIONS
  Even in clinical laboratories, the technical performance of genotyping in EGFR mutation testing for NSCLC can be improved, evident from a high level of diagnostic errors. Robust EQA can contribute to global optimisation of EGFR testing for NSCLC patients.
authors.affiliation: EMQN, Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester M13 9WL, UK.
authors.forename: S
authors.initials: S
authors.lastname: Patton
authors.affiliation: Cell Biology and Biotherapy Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale'-IRCCS, 80131 Naples, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Normanno
authors.affiliation: Christie Hospital, Manchester M20 4BX, UK.
authors.forename: F
authors.initials: F
authors.lastname: Blackhall
authors.affiliation: Biomarker Solutions Ltd, London EC1V 2NX, UK.
authors.forename: S
authors.initials: S
authors.lastname: Murray
authors.affiliation: Department of Pathology, Aberdeen Royal Infirmary, Aberdeen AB25 2ZN, UK.
authors.forename: K M
authors.initials: KM
authors.lastname: Kerr
authors.affiliation: Charité, Humboldt-Universität zu Berlin, Berlin 10117, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Dietel
authors.affiliation: Medical University of Vienna, 1010 Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Filipits
authors.affiliation: Pangaea Biotech, USP Dexeus University Institute, Barcelona 08028, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Benlloch
authors.affiliation: Royal Marsden Hospital, London SW3 6JJ, UK.
authors.forename: S
authors.initials: S
authors.lastname: Popat
authors.affiliation: University Hospital Zürich, CH-8091 Zürich, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Stahel
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam 1081 HZ, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Thunnissen
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics*; D009154:Mutation; D011786:Quality Control
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors