{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T15:04:32Z","timestamp":1770822272838,"version":"3.50.1"},"reference-count":38,"publisher":"Archives of Pathology and Laboratory Medicine","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,9]]},"abstract":"\n Context<\/jats:italic>\n .\u2014The addition of cetuximab to first-line chemotherapy substantially prolonged survival in patients with advanced non\u2013small cell lung cancer whose tumors expressed high levels of epidermal growth factor receptor (EGFR; immunohistochemistry score of \u2265200 on a scale of 0\u2013300).\n <\/jats:p>\n \n Objective<\/jats:italic>\n .\u2014To evaluate the interobserver reproducibility of this EGFR immunohistochemistry scoring system, based on both the tumor cell membrane staining intensity (graded 0\u20133+) and the percentage of cells staining at each intensity.\n <\/jats:p>\n \n Design<\/jats:italic>\n .\u2014In parts 1 (initial feasibility study) and 2 of this 2-part round robin test, sections of different non\u2013small 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\u2013 (<200) and high\u2013 (\u2265200) EGFR expression groups.\n <\/jats:p>\n \n Results<\/jats:italic>\n .\u2014After 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 \u03ba 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.\n <\/jats:p>\n \n Conclusions<\/jats:italic>\n .\u2014After appropriate training, assessing EGFR expression by this immunohistochemistry-based method allowed a highly reproducible allocation of non\u2013small cell lung cancers into clinically relevant high\u2013 or low\u2013EGFR expression groups.\n <\/jats:p>","DOI":"10.5858\/arpa.2012-0605-oa","type":"journal-article","created":{"date-parts":[[2012,12,27]],"date-time":"2012-12-27T10:55:04Z","timestamp":1356605704000},"page":"1255-1261","source":"Crossref","is-referenced-by-count":22,"title":["Reproducibility of Immunohistochemical Scoring for Epidermal Growth Factor Receptor Expression in Non\u2013Small Cell Lung Cancer: Round Robin Test"],"prefix":"10.5858","volume":"137","author":[{"given":"Josef","family":"R\u00fcschoff","sequence":"first","affiliation":[{"name":"From the Department of \u2009Pathology, Institute of Pathology Nordhessen, Kassel, Germany (Drs R\u00fcschoff and Middel); Targos Advance AG, Kassel, Germany (Drs R\u00fcschoff and Middel); the \u2009Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom (Dr Kerr); \u2009Histopathology Biomarker Technologies, Merck KGaA, Darmstadt, Germany (Dr Grote); \u2009Global Biostatistics, Merck KGaA, Darmstadt, Germany (Dr von Heydebreck); the Department of Pathology..."}]},{"given":"Keith M.","family":"Kerr","sequence":"additional","affiliation":[{"name":"From the Department of \u2009Pathology, Institute of Pathology Nordhessen, Kassel, Germany (Drs R\u00fcschoff and Middel); Targos Advance AG, Kassel, Germany (Drs R\u00fcschoff and Middel); the \u2009Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom (Dr Kerr); \u2009Histopathology Biomarker Technologies, Merck KGaA, Darmstadt, Germany (Dr Grote); \u2009Global Biostatistics, Merck KGaA, Darmstadt, Germany (Dr von Heydebreck); the Department of Pathology..."}]},{"given":"Hans J.","family":"Grote","sequence":"additional","affiliation":[{"name":"From the Department of \u2009Pathology, Institute of Pathology Nordhessen, Kassel, Germany (Drs R\u00fcschoff and Middel); Targos Advance AG, Kassel, Germany (Drs R\u00fcschoff and Middel); the \u2009Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom (Dr Kerr); \u2009Histopathology Biomarker Technologies, Merck KGaA, Darmstadt, Germany (Dr Grote); \u2009Global Biostatistics, Merck KGaA, Darmstadt, Germany (Dr von Heydebreck); the Department of Pathology..."}]},{"given":"Peter","family":"Middel","sequence":"additional","affiliation":[{"name":"From the Department of \u2009Pathology, Institute of Pathology Nordhessen, Kassel, Germany (Drs R\u00fcschoff and Middel); Targos Advance AG, Kassel, Germany (Drs R\u00fcschoff and Middel); the \u2009Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom (Dr Kerr); \u2009Histopathology Biomarker Technologies, Merck KGaA, Darmstadt, Germany (Dr Grote); \u2009Global Biostatistics, Merck KGaA, Darmstadt, Germany (Dr von Heydebreck); the Department of Pathology..."}]},{"given":"Anja","family":"von Heydebreck","sequence":"additional","affiliation":[{"name":"From the Department of \u2009Pathology, Institute of Pathology Nordhessen, Kassel, Germany (Drs R\u00fcschoff and Middel); Targos Advance AG, Kassel, Germany (Drs R\u00fcschoff and Middel); the \u2009Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom (Dr Kerr); \u2009Histopathology Biomarker Technologies, Merck KGaA, Darmstadt, Germany (Dr Grote); \u2009Global Biostatistics, Merck KGaA, Darmstadt, Germany (Dr von Heydebreck); the Department of Pathology..."}]},{"given":"Ven\u00e2ncio A.","family":"Alves","sequence":"additional","affiliation":[{"name":"From the Department of \u2009Pathology, Institute of Pathology Nordhessen, Kassel, Germany (Drs R\u00fcschoff and Middel); Targos Advance AG, Kassel, Germany (Drs R\u00fcschoff and Middel); the \u2009Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom (Dr Kerr); \u2009Histopathology Biomarker Technologies, Merck KGaA, Darmstadt, Germany (Dr Grote); \u2009Global Biostatistics, Merck KGaA, Darmstadt, Germany (Dr von Heydebreck); the Department of Pathology..."}]},{"given":"Stephan E.","family":"Baldus","sequence":"additional","affiliation":[{"name":"From the Department of \u2009Pathology, Institute of Pathology Nordhessen, Kassel, Germany (Drs R\u00fcschoff and Middel); Targos Advance AG, Kassel, Germany (Drs R\u00fcschoff and Middel); the \u2009Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom (Dr Kerr); \u2009Histopathology Biomarker Technologies, Merck KGaA, Darmstadt, Germany (Dr Grote); \u2009Global Biostatistics, Merck KGaA, Darmstadt, Germany (Dr von Heydebreck); the Department of Pathology..."}]},{"given":"Reinhard","family":"B\u00fcttner","sequence":"additional","affiliation":[{"name":"From the Department of \u2009Pathology, Institute of Pathology Nordhessen, Kassel, Germany (Drs R\u00fcschoff and Middel); Targos Advance AG, Kassel, Germany (Drs R\u00fcschoff and Middel); the \u2009Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom (Dr Kerr); \u2009Histopathology Biomarker Technologies, Merck KGaA, Darmstadt, Germany (Dr Grote); \u2009Global Biostatistics, Merck KGaA, Darmstadt, Germany (Dr von Heydebreck); the Department of Pathology..."}]},{"given":"Lina","family":"Carvalho","sequence":"additional","affiliation":[{"name":"From the Department of \u2009Pathology, Institute of Pathology Nordhessen, Kassel, Germany (Drs R\u00fcschoff and Middel); Targos Advance AG, Kassel, Germany (Drs R\u00fcschoff and Middel); the \u2009Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom (Dr Kerr); \u2009Histopathology Biomarker Technologies, Merck KGaA, Darmstadt, Germany (Dr Grote); \u2009Global Biostatistics, Merck KGaA, Darmstadt, Germany (Dr von Heydebreck); the Department of Pathology..."}]},{"given":"Ludger","family":"Fink","sequence":"additional","affiliation":[{"name":"From the Department of \u2009Pathology, Institute of Pathology Nordhessen, Kassel, Germany (Drs R\u00fcschoff and Middel); Targos Advance AG, Kassel, Germany (Drs R\u00fcschoff and Middel); the \u2009Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom (Dr Kerr); \u2009Histopathology Biomarker Technologies, Merck KGaA, Darmstadt, Germany (Dr Grote); \u2009Global Biostatistics, Merck KGaA, Darmstadt, Germany (Dr von Heydebreck); the Department of Pathology..."}]},{"given":"Wolfram","family":"Jochum","sequence":"additional","affiliation":[{"name":"From the Department of \u2009Pathology, Institute of Pathology Nordhessen, Kassel, Germany (Drs R\u00fcschoff and Middel); Targos Advance AG, Kassel, Germany (Drs R\u00fcschoff and Middel); the \u2009Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom (Dr Kerr); \u2009Histopathology Biomarker Technologies, Merck KGaA, Darmstadt, Germany (Dr Grote); \u2009Global Biostatistics, Merck KGaA, Darmstadt, Germany (Dr von Heydebreck); the Department of Pathology..."}]},{"given":"Anthony W. I.","family":"Lo","sequence":"additional","affiliation":[{"name":"From the Department of \u2009Pathology, Institute of Pathology Nordhessen, Kassel, Germany (Drs R\u00fcschoff and Middel); Targos Advance AG, Kassel, Germany (Drs R\u00fcschoff and Middel); the \u2009Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom (Dr Kerr); \u2009Histopathology Biomarker Technologies, Merck KGaA, Darmstadt, Germany (Dr Grote); \u2009Global Biostatistics, Merck KGaA, Darmstadt, Germany (Dr von Heydebreck); the Department of Pathology..."}]},{"given":"Fernando","family":"L\u00f3pez-R\u00edos","sequence":"additional","affiliation":[{"name":"From the Department of \u2009Pathology, Institute of Pathology Nordhessen, Kassel, Germany (Drs R\u00fcschoff and Middel); Targos Advance AG, Kassel, Germany (Drs R\u00fcschoff and Middel); the \u2009Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom (Dr Kerr); \u2009Histopathology Biomarker Technologies, Merck KGaA, Darmstadt, Germany (Dr Grote); \u2009Global Biostatistics, Merck KGaA, Darmstadt, Germany (Dr von Heydebreck); the Department of Pathology..."}]},{"given":"Alexander","family":"Marx","sequence":"additional","affiliation":[{"name":"From the Department of \u2009Pathology, Institute of Pathology Nordhessen, Kassel, Germany (Drs R\u00fcschoff and Middel); Targos Advance AG, Kassel, Germany (Drs R\u00fcschoff and Middel); the \u2009Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom (Dr Kerr); \u2009Histopathology Biomarker Technologies, Merck KGaA, Darmstadt, Germany (Dr Grote); \u2009Global Biostatistics, Merck KGaA, Darmstadt, Germany (Dr von Heydebreck); the Department of Pathology..."}]},{"given":"Thierry J.","family":"Molina","sequence":"additional","affiliation":[{"name":"From the Department of \u2009Pathology, Institute of Pathology Nordhessen, Kassel, Germany (Drs R\u00fcschoff and Middel); Targos Advance AG, Kassel, Germany (Drs R\u00fcschoff and Middel); the \u2009Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom (Dr Kerr); \u2009Histopathology Biomarker Technologies, Merck KGaA, Darmstadt, Germany (Dr Grote); \u2009Global Biostatistics, Merck KGaA, Darmstadt, Germany (Dr von Heydebreck); the Department of Pathology..."}]},{"given":"W\u0142odzimierz T.","family":"Olszewski","sequence":"additional","affiliation":[{"name":"From the Department of \u2009Pathology, Institute of Pathology Nordhessen, Kassel, Germany (Drs R\u00fcschoff and Middel); Targos Advance AG, Kassel, Germany (Drs R\u00fcschoff and Middel); the \u2009Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom (Dr Kerr); \u2009Histopathology Biomarker Technologies, Merck KGaA, Darmstadt, Germany (Dr Grote); \u2009Global Biostatistics, Merck KGaA, Darmstadt, Germany (Dr von Heydebreck); the Department of Pathology..."}]},{"given":"Ralf J.","family":"Rieker","sequence":"additional","affiliation":[{"name":"From the Department of \u2009Pathology, Institute of Pathology Nordhessen, Kassel, Germany (Drs R\u00fcschoff and Middel); Targos Advance AG, Kassel, Germany (Drs R\u00fcschoff and Middel); the \u2009Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom (Dr Kerr); \u2009Histopathology Biomarker Technologies, Merck KGaA, Darmstadt, Germany (Dr Grote); \u2009Global Biostatistics, Merck KGaA, Darmstadt, Germany (Dr von Heydebreck); the Department of Pathology..."}]},{"given":"Marco","family":"Volante","sequence":"additional","affiliation":[{"name":"From the Department of \u2009Pathology, Institute of Pathology Nordhessen, Kassel, Germany (Drs R\u00fcschoff and Middel); Targos Advance AG, Kassel, Germany (Drs R\u00fcschoff and Middel); the \u2009Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom (Dr Kerr); \u2009Histopathology Biomarker Technologies, Merck KGaA, Darmstadt, Germany (Dr Grote); \u2009Global Biostatistics, Merck KGaA, Darmstadt, Germany (Dr von Heydebreck); the Department of Pathology..."}]},{"given":"Erik","family":"Thunnissen","sequence":"additional","affiliation":[{"name":"From the Department of \u2009Pathology, Institute of Pathology Nordhessen, Kassel, Germany (Drs R\u00fcschoff and Middel); Targos Advance AG, Kassel, Germany (Drs R\u00fcschoff and Middel); the \u2009Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom (Dr Kerr); \u2009Histopathology Biomarker Technologies, Merck KGaA, Darmstadt, Germany (Dr Grote); \u2009Global Biostatistics, Merck KGaA, Darmstadt, Germany (Dr von Heydebreck); the Department of Pathology..."}]},{"given":"Fritz","family":"Wrba","sequence":"additional","affiliation":[{"name":"From the Department of \u2009Pathology, Institute of Pathology Nordhessen, Kassel, Germany (Drs R\u00fcschoff and Middel); Targos Advance AG, Kassel, Germany (Drs R\u00fcschoff and Middel); the \u2009Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom (Dr Kerr); \u2009Histopathology Biomarker Technologies, Merck KGaA, Darmstadt, Germany (Dr Grote); \u2009Global Biostatistics, Merck KGaA, Darmstadt, Germany (Dr von Heydebreck); the Department of Pathology..."}]},{"given":"Ilhan","family":"Celik","sequence":"additional","affiliation":[{"name":"From the Department of \u2009Pathology, Institute of Pathology Nordhessen, Kassel, Germany (Drs R\u00fcschoff and Middel); Targos Advance AG, Kassel, Germany (Drs R\u00fcschoff and Middel); the \u2009Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom (Dr Kerr); \u2009Histopathology Biomarker Technologies, Merck KGaA, Darmstadt, Germany (Dr Grote); \u2009Global Biostatistics, Merck KGaA, Darmstadt, Germany (Dr von Heydebreck); the Department of Pathology..."}]},{"given":"Stephan","family":"St\u00f6rkel","sequence":"additional","affiliation":[{"name":"From the Department of \u2009Pathology, Institute of Pathology Nordhessen, Kassel, Germany (Drs R\u00fcschoff and Middel); Targos Advance AG, Kassel, Germany (Drs R\u00fcschoff and Middel); the \u2009Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom (Dr Kerr); \u2009Histopathology Biomarker Technologies, Merck KGaA, Darmstadt, Germany (Dr Grote); \u2009Global Biostatistics, Merck KGaA, Darmstadt, Germany (Dr von Heydebreck); the Department of Pathology..."}]}],"member":"3906","reference":[{"issue":"9674","key":"i1543-2165-137-9-1255-b01","series-title":"Lancet","first-page":"1525","article-title":"Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial","volume":"373","author":"Pirker\n R,","year":"2009","unstructured":"Pirker\n R, \n \n Pereira\n JR, \n \n Szczesna\n A, \n et al\n . 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