Arch Pathol Lab Med. 2012 Dec 27. [Epub ahead of print]
Reproducibility of Immunohistochemical Scoring for Epidermal Growth Factor Receptor Expression in Non-Small Cell Lung Cancer.
Rüschoff J, Kerr KM, Grote HJ, Middel P, von Heydebreck A, Alves VA, Baldus SE, Büttner R, Carvalho L, Fink L, Jochum W, Lo AW, López-Ríos F, Marx A, Molina TJ, Olszewski WT, Rieker RJ, Volante M, Thunnissen E, Wrba F, Celik I, Störkel S.
Source
From the Department of Pathology, Institute of Pathology Nordhessen, Kassel, Germany (Drs Rüschoff and Middel); Targos Advance AG, Kassel, Germany (Drs Rüschoff and Middel); the Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom (Dr Kerr); Histopathology Biomarker Technologies, Merck KGaA, Darmstadt, Germany (Dr Grote); Global Biostatistics, Merck KGaA, Darmstadt, Germany (Dr von Heydebreck); the Department of Pathology, LIM14-University of São Paulo School of Medicine & CICAP-Pathology, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil (Dr Alves); the Institute of Pathology, University Hospital Düsseldorf, Düsseldorf, Germany (Dr Baldus); the Institute of Pathology, University Hospital Cologne, Cologne, Germany (Dr Büttner); the Department of Pathology, Hospitais da Universidade de Coimbra, Coimbra, Portugal (Dr Carvalho); the Institute of Pathology and Cytology, Interregional Group Practice, Wetzlar, Germany (Dr Fink); the Institute of Pathology, Kantonsspital St Gallen, St Gallen, Switzerland (Dr Jochum); the Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China (Dr Lo); the Laboratory of Therapeutic Targets, Hospital Universitario Madrid Sanchinarro, Madrid, Spain (Dr López-Ríos); the Department of Pathology, University Hospital of Mannheim, Mannheim, Germany (Dr Marx); the Department of Anatomy and Cytology, Université Paris Descartes, Paris, France (Dr Molina); the Department of Pathology, Institute of Oncology, Warsaw, Poland (Dr Olszewski); Institute for Pathology, University Hospital, Erlangen, Germany (Dr Rieker); the Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Turin, Italy (Mr Volante); the Department of Pathology, VU Medical Centre, Amsterdam, The Netherlands (Dr Thunnissen); the Department of Pathology, Clinical Institute of Pathology, Vienna, Austria (Dr Wrba); the Global Clinical Development Unit Oncology, Merck KGaA, Darmstadt, Germany (Dr Celik); and the Institute of Pathology, University of Witten/Herdecke and HELIOS Hospital Wuppertal, Wuppertal, Germany (Dr Störkel).
Abstract
Context.-The addition of cetuximab to first-line chemotherapy substantially prolonged survival in patients with advanced non-small cell lung cancerwhose tumors expressed high levels of epidermal growth factor receptor (EGFR; immunohistochemistry score of ≥200 on a scale of 0-300).
Objective.-To evaluate the interobserver reproducibility of this EGFR immunohistochemistry scoring system, based on both the tumor cell membrane staining intensity (graded 0-3+) and the percentage of cells staining at each intensity.
Design.-In parts 1 (initial feasibility study) and 2 of this 2-part round robin test, sections of different non-small cell lung cancer tissue microarrays were stained in a central reference laboratory. Following reference evaluation, EGFR expression in 30 selected tumor cores was characterized in serial sections by lung cancer pathology specialists. The reproducibility of scoring by different raters was assessed. Analysis of between-rater agreement was based on the allocation of EGFR immunohistochemistry scores into low- (<200) and high- (≥200) EGFR expression groups.
Results.-After discussion with raters of the issues impacting reproducibility identified in part 1 and following adjustment of processes, part 2 of the round robin test showed a high interobserver agreement in EGFR immunohistochemistry scoring, with an overall concordance rate of 90.9% and a mean κ coefficient of 0.812. Specimens with a reference EGFR immunohistochemistry score of lower than 200 and of 200 or higher showed mean concordance rates of 94.7% and 85.6%, respectively.
Conclusions.-After appropriate training, assessing EGFR expression by this immunohistochemistry-based method allowed a highly reproducible allocation of non-small cell lung cancers into clinically relevant high- or low-EGFR expression groups.
Objective.-To evaluate the interobserver reproducibility of this EGFR immunohistochemistry scoring system, based on both the tumor cell membrane staining intensity (graded 0-3+) and the percentage of cells staining at each intensity.
Design.-In parts 1 (initial feasibility study) and 2 of this 2-part round robin test, sections of different non-small cell lung cancer tissue microarrays were stained in a central reference laboratory. Following reference evaluation, EGFR expression in 30 selected tumor cores was characterized in serial sections by lung cancer pathology specialists. The reproducibility of scoring by different raters was assessed. Analysis of between-rater agreement was based on the allocation of EGFR immunohistochemistry scores into low- (<200) and high- (≥200) EGFR expression groups.
Results.-After discussion with raters of the issues impacting reproducibility identified in part 1 and following adjustment of processes, part 2 of the round robin test showed a high interobserver agreement in EGFR immunohistochemistry scoring, with an overall concordance rate of 90.9% and a mean κ coefficient of 0.812. Specimens with a reference EGFR immunohistochemistry score of lower than 200 and of 200 or higher showed mean concordance rates of 94.7% and 85.6%, respectively.
Conclusions.-After appropriate training, assessing EGFR expression by this immunohistochemistry-based method allowed a highly reproducible allocation of non-small cell lung cancers into clinically relevant high- or low-EGFR expression groups.
