title: Interobserver agreement and assay reproducibility of folate receptor α expression in lung adenocarcinoma: a prognostic marker and potential therapeutic target.
abstract: BACKGROUND
  Lung cancer is the leading cause of cancer deaths in the United States and globally. Folate-targeted drugs are among the promising new targeted therapies for lung cancer, provided predictive biomarkers can be identified for optimal patient selection.
  
  
  OBJECTIVE
  To evaluate the interobserver agreement and reproducibility of an immunohistochemistry assay for folate receptor α as a potential predictive marker for folate-targeted therapies.
  
  
  METHODS
  Immunohistochemistry using anti-folate receptor α antibody 26B3 was performed on formalin-fixed, paraffin-embedded tissues. The M-score, a semiquantitative measure of staining intensity and proportion of tumor cells staining, was determined for each specimen. Interobserver agreement was assessed using lung adenocarcinoma specimens stained at a single site and evaluated by 3 independent pathologists. Interinstrument reproducibility assessed 20 specimens stained by 3 different automated stainers. Interlaboratory agreement was determined on 5 specimens, repeatedly stained on each of 5 days, at 3 different study sites.
  
  
  RESULTS
  Folate receptor α expression was identified in 39 of 54 cases of lung adenocarcinoma (72%) and 4 of 37 cases of lung squamous cell carcinoma (11%). Agreement among 3 pathologists was found in 24 of 26 cases (92%). Interinstrument reproducibility was observed in 19 of 20 cases (95%). Agreement among 3 laboratories was found for 49 of 50 specimens (98%).
  
  
  CONCLUSIONS
  Immunostaining of folate receptor α in lung adenocarcinomas is reproducible across staining platforms and among laboratories. Agreement among pathologists is achieved using a semiquantitative scoring method. An accurate and convenient method for determining folate receptor α expression offers a potentially invaluable tool for selecting patients for folate-targeted therapies.
authors.affiliation: From the Department of Research & Development, Biocare Medical LLC, Concord, California (Drs Bremer and Tacha and Ms Scoggin); and the Department of Diagnostic Development, Morphotek Inc, Exton, Pennsylvania (Ms Somers and Dr O'Shannessy).
authors.forename: Ryan E
authors.initials: RE
authors.lastname: Bremer
authors.forename: Tatiana S
authors.initials: TS
authors.lastname: Scoggin
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Somers
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: O'Shannessy
authors.forename: David E
authors.initials: DE
authors.lastname: Tacha
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D003937:Diagnosis, Differential; D058975:Folate Receptor 1 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism*; D015588:Observer Variation; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D058975:Folate Receptor 1