title: Immunohistochemistry for EGFR Mutation Detection in Non-Small-Cell Lung Cancer.
abstract: The sensitivity and specificity of immunohistochemistry (IHC) was compared with the standard polymerase chain reaction (PCR)-based method for detecting common activating epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC). Additionally, we evaluated predictive value of IHC EGFR mutation-positive status for EGFR tyrosine kinase inhibitor (TKI) treatment outcome and estimated cost-effectiveness for the upfront IHC testing.
  
  
  
  The trial included 79 consecutive EGFR mutation-positive and 29 EGFR mutation-negative NSCLC cases diagnosed with reflex PCR-based testing. Two mutation-specific antibodies against the most common exon 19 deletion, namely E746-A750del (clone SP111) and L858R mutation (clone SP125) were tested by using automated immunostainer. Sixty of 79 EGFR mutation-positive cases were treated with EGFR TKIs for advanced disease and included in treatment outcome analysis. A decision tree was used for the cost-effectiveness analysis.
  
  
  
  The overall sensitivity and specificity of the IHC-based method compared with the PCR-based method were 84.8% (95% confidence interval [CI] 74.6-91.6) and 100% (95% CI 85.4-100), respectively. The median progression-free survival (PFS) and overall survival (OS) of patients with IHC-positive EGFR mutation status were highly comparable to the total cohort (PFS: 14.3 vs. 14.0 months; OS: 34.4 vs. 34.4 months). The PCR and IHC cost ratio needs to be approximately 8-to-1 and 4-to-1 in White and Asian populations, respectively, to economically justify upfront use of IHC.
  
  
  
  The trial confirmed an excellent specificity with fairly good sensitivity of IHC with mutation-specific antibodies for common EGFR mutations and the accuracy of IHC testing for predicting response to EGFR TKIs. The use of upfront IHC depends mainly on the population EGFR mutation positivity probability.
authors.affiliation: University Clinic Golnik, Golnik, Slovenia. Electronic address: nina.turnsek@klinika-golnik.si.
authors.forename: Nina Turnšek
authors.initials: NT
authors.lastname: Hitij
authors.affiliation: University Clinic Golnik, Golnik, Slovenia.
authors.forename: Izidor
authors.initials: I
authors.lastname: Kern
authors.affiliation: Faculty of Computer and Information Science, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Sadikov
authors.affiliation: University Clinic Golnik, Golnik, Slovenia.
authors.forename: Lea
authors.initials: L
authors.lastname: Knez
authors.affiliation: Institute of Oncology, Ljubljana, Slovenia.
authors.forename: Karmen
authors.initials: K
authors.lastname: Stanič
authors.affiliation: Institute of Oncology, Ljubljana, Slovenia.
authors.forename: Matjaž
authors.initials: M
authors.lastname: Zwitter
authors.affiliation: University Clinic Golnik, Golnik, Slovenia; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Tanja
authors.initials: T
authors.lastname: Cufer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D003362:Cost-Benefit Analysis; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005240:Feasibility Studies; D006801:Humans; D007150:Immunohistochemistry / Q000191:economics / Q000379:methods*; D008168:Lung / Q000502:physiology*; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D016019:Survival Analysis
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Cost-effectiveness; Epidermal growth factor receptor mutation; Mutation-specific antibodies; NSCLC; Survival