title: Novel epidermal growth factor receptor mutation-specific antibodies for non-small cell lung cancer: immunohistochemistry as a possible screening method for epidermal growth factor receptor mutations.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) predict better outcome to EGFR tyrosine kinase inhibitors. The most common mutations are exon 19 deletions (most frequently E746-A750) and L858R point mutation in exon 21. Here, we evaluated the accuracy of novel EGFR mutation-specific antibodies in a Japanese cohort with NSCLC and compared with direct DNA sequencing and clinical outcome.
  
  
  METHODS
  Immunohistochemistry (IHC) using antibodies specific for the E746-A750 and L858R mutations in EGFR was performed on tissue microarrays of tumors from 70 gefitinib treated NSCLC patients. Extracted DNA was sequenced for mutational analysis of EGFR exons 18 to 21.
  
  
  RESULTS
  DNA sequencing showed EGFR mutations in 41 patients (58.6%) and exon 19 deletions in 18 patients (25.7%), 11 of 18 (61%) had a deletion in the range of E746-A750 and 12 (17.1%) had exon 21 mutations (L858R). IHC showed, for the E746-A750 and L858R mutations, sensitivity (81.8 and 75%), specificity (100 and 96.6%), positive predictive value (100 and 81.8%), and negative predictive value (96.7 and 94.9%). Analysis for objective response rates and survival were not correlated to IHC staining, although the combined staining showed nonsignificant trends toward better overall survival for patients with EGFR mutations.
  
  
  CONCLUSIONS
  The mutation-specific IHC antibodies have high sensitivity and specificity for predefined EFGR mutations and may be suitable for screening for these predefined mutations. However, negative IHC results require further mutation analyses before excluding EGFR-targeted therapy.
authors.affiliation: Division of Medical Oncology, University of Colorado Denver, Aurora, Colorado 80045, USA.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kato
authors.forename: Nir
authors.initials: N
authors.lastname: Peled
authors.forename: Murry W
authors.initials: MW
authors.lastname: Wynes
authors.forename: Koichi
authors.initials: K
authors.lastname: Yoshida
authors.forename: Marta
authors.initials: M
authors.lastname: Pardo
authors.forename: Celine
authors.initials: C
authors.lastname: Mascaux
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ohira
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuboi
authors.forename: Jun
authors.initials: J
authors.lastname: Matsubayashi
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nagao
authors.forename: Norihiko
authors.initials: N
authors.lastname: Ikeda
authors.forename: Fred R
authors.initials: FR
authors.lastname: Hirsch
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology*; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D015331:Cohort Studies; D004273:DNA, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D046888:Tissue Array Analysis
chemical_list: D000911:Antibodies, Monoclonal; D004273:DNA, Neoplasm; C512478:EGFR protein, human; D066246:ErbB Receptors