title: Reproducibility of immunohistochemical scoring for epidermal growth factor receptor expression in non-small cell lung cancer: round robin test.
abstract: BACKGROUND
  The addition of cetuximab to first-line chemotherapy substantially prolonged survival in patients with advanced non-small cell lung cancer whose 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.
  
  
  METHODS
  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.
authors.affiliation: Department of  Pathology, Institute of Pathology Nordhessen, Kassel, Germany. rueschoff@patho-nordhessen.de
authors.forename: Josef
authors.initials: J
authors.lastname: Rüschoff
authors.forename: Keith M
authors.initials: KM
authors.lastname: Kerr
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Grote
authors.forename: Peter
authors.initials: P
authors.lastname: Middel
authors.forename: Anja
authors.initials: A
authors.lastname: von Heydebreck
authors.forename: Venâncio A
authors.initials: VA
authors.lastname: Alves
authors.forename: Stephan E
authors.initials: SE
authors.lastname: Baldus
authors.forename: Reinhard
authors.initials: R
authors.lastname: Büttner
authors.forename: Lina
authors.initials: L
authors.lastname: Carvalho
authors.forename: Ludger
authors.initials: L
authors.lastname: Fink
authors.forename: Wolfram
authors.initials: W
authors.lastname: Jochum
authors.forename: Anthony W I
authors.initials: AW
authors.lastname: Lo
authors.forename: Fernando
authors.initials: F
authors.lastname: López-Ríos
authors.forename: Alexander
authors.initials: A
authors.lastname: Marx
authors.forename: Thierry J
authors.initials: TJ
authors.lastname: Molina
authors.forename: Włodzimierz T
authors.initials: WT
authors.lastname: Olszewski
authors.forename: Ralf J
authors.initials: RJ
authors.lastname: Rieker
authors.forename: Marco
authors.initials: M
authors.lastname: Volante
authors.forename: Erik
authors.initials: E
authors.lastname: Thunnissen
authors.forename: Fritz
authors.initials: F
authors.lastname: Wrba
authors.forename: Ilhan
authors.initials: I
authors.lastname: Celik
authors.forename: Stephan
authors.initials: S
authors.lastname: Störkel
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D015588:Observer Variation; D011446:Prospective Studies; D015203:Reproducibility of Results; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors