title: Epidermal growth factor receptor mutation-specific immunohistochemical antibodies in lung adenocarcinoma.
abstract: OBJECTIVE
  We investigated the sensitivity and specificity of two novel Epidermal growth factor receptor (EGFR) mutation-specific antibodies in the detection of the most common EGFR mutations in lung adenocarcinoma.
  
  
  RESULTS
  A total of 241 resected lung adenocarcinoma specimens and six resected post-neoadjuvant gefitinib adenocarcinomas were analysed for EGFR mutation using mass spectrometry, fragment analysis and direct PCR sequencing platforms. Tissue arrays and/or full sections of these cases were evaluated using immunohistochemistry with two novel antibodies (clones SP125 and SP111) and two previously reported antibodies (clones 43B2 and 6B6), specific for L858R or 15-nucleotide exon-19 deletion EGFR mutations. SP125 antibody detected EGFR L858R mutation with a sensitivity of 76% and positive predictive value of 73%. SP111 antibody stained the 15-nucleotide EGFR exon-19 deletions with a sensitivity of 83% and a positive predictive value of 94%. Pretreatment with gefitinib did not affect antibody performance. Full-section immunohistochemical staining detected heterogeneous mutant EGFR proteins expression in tumours, and revealed L858R mutation in the non-neoplastic bronchial epithelium adjacent to EGFR L858R-carrying carcinomas in three of 16 (19%) cases.
  
  
  CONCLUSIONS
  Immunohistochemistry using EGFR mutant-specific antibodies may be useful in shortening the diagnostic time of lung adenocarcinoma with most common EGFR mutations, especially in samples with low tumour cellularity.
authors.affiliation: Department of Pathology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Ghassan
authors.initials: G
authors.lastname: Allo
authors.forename: Bizhan
authors.initials: B
authors.lastname: Bandarchi
authors.forename: Naoki
authors.initials: N
authors.lastname: Yanagawa
authors.forename: Ami
authors.initials: A
authors.lastname: Wang
authors.forename: Warren
authors.initials: W
authors.lastname: Shih
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Morgan
authors.initials: M
authors.lastname: Dalby
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nitta
authors.forename: Christine
authors.initials: C
authors.lastname: To
authors.forename: Ni
authors.initials: N
authors.lastname: Liu
authors.forename: Jenna
authors.initials: J
authors.lastname: Sykes
authors.forename: Ming S
authors.initials: MS
authors.lastname: Tsao
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012680:Sensitivity and Specificity
chemical_list: D000906:Antibodies; D066246:ErbB Receptors
keywords: epidermal growth factor receptor; immunohistochemistry; lung adenocarcinoma; mutation