title: Ascertaining an appropriate diagnostic algorithm using EGFR mutation-specific antibodies to detect EGFR status in non-small-cell lung cancer.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) mutation status is the most valuable indicator in the screening of non-small-cell lung cancer (NSCLC) patients for tyrosine kinase inhibitor (TKI) therapy. Accurate, rapid and economical methods of detecting EGFR mutations have become important. The use of two mutation-specific antibodies targeting the delE746-A750 mutation in exon 19 and L858R mutation in exon 21 makes this task possible, but the lack of consensually acceptable criteria for positive results limits the application of this antibody based mutation detection.
  
  
  METHODS
  We collected 399 specimens from NSCLC patients (145 resection specimens, 220 biopsy specimens, and 34 cytology specimens) whose EGFR mutation status had been detected by TaqMan PCR assay. Immunohistochemical (IHC) analyses using EGFR mutation-specific antibodies were employed for all samples. After staining and scoring, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated in accordance with different levels of positive grades in comparison with the results of PCR-based assay.
  
  
  RESULTS
  In IHC-based analyses, 144 cases were scored 0, 104 cases were scored 1+, 103 cases were scored 2+, and 48 cases were scored 3+. With the molecular-based results were set as the "gold standard", the prevalence of mutation was 6.94% (10/144), 23.08% (24/104), 67.96% (70/103) and 100% (48/48), respectively, for samples with scores 0, 1+, 2+ and 3+. When score 3+ was considered positive, the specificity and PPV were 100%; if only score 0 was considered negative, 93.06% NPV was obtained.
  
  
  CONCLUSIONS
  Patients with score 3+ have a perfect PPV (100%), and may accept TKI treatment directly without any molecular-based assays. Patients with score 0 had high NPV (93.06%), which could reach 97.22% when the detection of total EGFR was applied. However, samples with score 1+ or 2+ are unreliable and need further verification of EGFR mutation status by molecular-based assays.
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.
authors.forename: Guiyang
authors.initials: G
authors.lastname: Jiang
authors.forename: Chuifeng
authors.initials: C
authors.lastname: Fan
authors.forename: Xiupeng
authors.initials: X
authors.lastname: Zhang
authors.forename: Qianze
authors.initials: Q
authors.lastname: Dong
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Shundong
authors.initials: S
authors.lastname: Dai
authors.forename: Lianhe
authors.initials: L
authors.lastname: Yang
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Juanhan
authors.initials: J
authors.lastname: Yu
authors.forename: Enhua
authors.initials: E
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation
chemical_list: D066246:ErbB Receptors
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