Immunohistochemistry for EGFR Mutation Detection in Non-Small-Cell Lung Cancer

We evaluated the use of immunohistochemistry (IHC) for detection of epidermal growth factor receptor (EGFR) mutations in nonesmall-cell lung cancer on a cohort of 79 EGFR-mutated Whites. IHC demonstrated high accuracy for detection of common EGFR mutations as well as for predicting response to EGFR tyrosine kinase inhibitors as compared with standard polymerase chain reactionebased methodology. Cost-effective use of upfront IHC depends mainly on the population EGFR mutation positivity probability. Introduction: 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 nonesmall-cell lung cancer (NSCLC). Additionally, we evaluated predictive value of IHC EGFR mutatione positive status forEGFR tyrosine kinase inhibitor (TKI) treatment outcome and estimated cost-effectiveness for the upfront IHC testing. Methods: The trial included 79 consecutive EGFR mutationepositive and 29 EGFR mutatione 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 mutationepositive 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. Results: 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 progressionfree 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. Conclusion: 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. (C) 2016 Elsevier Inc. All rights reserved.