title: Sample features associated with success rates in population-based EGFR mutation testing.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) mutation testing has become critical in the treatment of patients with advanced non-small-cell lung cancer. This study involves a large cohort and epidemiologically unselected series of EGFR mutation testing for patients with nonsquamous non-small-cell lung cancer in a North American population to determine sample-related factors that influence success in clinical EGFR testing.
  
  
  METHODS
  Data from consecutive cases of Canadian province-wide testing at a centralized diagnostic laboratory for a 24-month period were reviewed. Samples were tested for exon-19 deletion and exon-21 L858R mutations using a validated polymerase chain reaction method with 1% to 5% detection sensitivity.
  
  
  RESULTS
  From 2651 samples submitted, 2404 samples were tested with 2293 samples eligible for analysis (1780 histology and 513 cytology specimens). The overall test-failure rate was 5.4% with overall mutation rate of 20.6%. No significant differences in the failure rate, mutation rate, or mutation type were found between histology and cytology samples. Although tumor cellularity was significantly associated with test-success or mutation rates in histology and cytology specimens, respectively, mutations could be detected in all specimen types. Significant rates of EGFR mutation were detected in cases with thyroid transcription factor (TTF)-1-negative immunohistochemistry (6.7%) and mucinous component (9.0%).
  
  
  CONCLUSIONS
  EGFR mutation testing should be attempted in any specimen, whether histologic or cytologic. Samples should not be excluded from testing based on TTF-1 status or histologic features. Pathologists should report the amount of available tumor for testing. However, suboptimal samples with a negative EGFR mutation result should be considered for repeat testing with an alternate sample.
authors.affiliation: Department of Pathology, University Health Network, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Pathology, Royal Columbian Hospital, New Westminster, British Columbia, Canada.
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Shiau
authors.affiliation: Department of Pathology, University Health Network, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jesse P
authors.initials: JP
authors.lastname: Babwah
authors.affiliation: Department of Pathology, University Health Network, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Gilda
authors.initials: G
authors.lastname: da Cunha Santos
authors.affiliation: Department of Biostatistics, University Health Network, and Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors.forename: Jenna R
authors.initials: JR
authors.lastname: Sykes
authors.affiliation: Department of Pathology, University Health Network, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Boerner
authors.affiliation: Department of Pathology, University Health Network, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: William R
authors.initials: WR
authors.lastname: Geddie
authors.affiliation: Division of Hematology and Medical Oncology, Princess Margaret Cancer Centre, and Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Natasha B
authors.initials: NB
authors.lastname: Leighl
authors.affiliation: Department of Pathology, University Health Network, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Cuihong
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Pathology, University Health Network, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kamel-Reid
authors.affiliation: Department of Pathology, University Health Network, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: David M
authors.initials: DM
authors.lastname: Hwang
authors.affiliation: Department of Pathology, University Health Network, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. Electronic address: ming.tsao@uhn.ca.
authors.forename: Ming-Sound
authors.initials: MS
authors.lastname: Tsao
mesh_terms: D001483:Base Sequence; D001707:Biopsy, Needle; D002170:Canada; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D003584:Cytological Techniques; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D008297:Male; D009687:Nuclear Proteins / Q000032:analysis; D011013:Pneumonectomy; D012189:Retrospective Studies; D017384:Sequence Deletion; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000032:analysis
chemical_list: C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D066246:ErbB Receptors