RT Journal Article
SR Electronic
T1 EGFR and KRAS quality assurance schemes in pathology: generating normative data for molecular predictive marker analysis in targeted therapy
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 884
OP 892
DO 10.1136/jclinpath-2011-200163
VO 64
IS 10
A1 Erik Thunnissen
A1 Judith V M G Bovée
A1 Hans Bruinsma
A1 Adriaan J C van den Brule
A1 Winand Dinjens
A1 Daniëlle A M Heideman
A1 Els Meulemans
A1 Petra Nederlof
A1 Carel van Noesel
A1 Clemens F M Prinsen
A1 Karen Scheidel
A1 Peter M van de Ven
A1 Roel de Weger
A1 Ed Schuuring
A1 Marjolijn Ligtenberg
YR 2011
UL http://jcp.bmj.com/content/64/10/884.abstract
AB Introduction The aim of this study was to compare the reproducibility of epidermal growth factor receptor (EGFR) immunohistochemistry (IHC), EGFR gene amplification analysis, and EGFR and KRAS mutation analysis among different laboratories performing routine diagnostic analyses in pathology in The Netherlands, and to generate normative data.Methods In 2008, IHC, in-situ hybridisation (ISH) for EGFR, and mutation analysis for EGFR and KRAS were tested. Tissue microarray sections were distributed for IHC and ISH, and tissue sections and isolated DNA with known mutations were distributed for mutation analysis. In 2009, ISH and mutation analysis were evaluated. False-negative and false-positive results were defined as different from the consensus, and sensitivity and specificity were estimated.Results In 2008, eight laboratories participated in the IHC ring study. In only 4/17 cases (23%) a consensus score of ≥75% was reached, indicating that this analysis was not sufficiently reliable to be applied in clinical practice. For EGFR ISH, and EGFR and KRAS mutation analysis, an interpretable result (success rate) was obtained in ≥97% of the cases, with mean sensitivity ≥96% and specificity ≥95%. For small sample proficiency testing, a norm was established defining outlier laboratories with unsatisfactory performance.Conclusions The result of EGFR IHC is not a suitable criterion for reliably selecting patients for anti-EGFR treatment. In contrast, molecular diagnostic methods for EGFR and KRAS mutation detection and EGFR ISH may be reliably performed with high accuracy, allowing treatment decisions for lung cancer.