title: EGFR gene status in cytological samples of nonsmall cell lung carcinoma: controversies and opportunities.
abstract: BACKGROUND
  In nonsmall cell lung cancer (NSCLC), the development and clinical application of tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) has required the investigation of EGFR status by gene copy number and/or mutation analysis. This review aimed to present the current knowledge of the use of cytological specimens for EGFR testing in lung cancer.
  
  
  METHODS
  A systematic computerized search was performed of the MEDLINE(R) and EMBASE databases to identify articles reporting the use of cytological samples for determining EGFR status in NSCLC.
  
  
  RESULTS
  Data were extracted from 30 original articles. An additional 19 reviews, consensus statements, and editorials were selected from 175 retrieved papers. Different techniques using cell blocks, scraped cells from archival slides, and fresh cells have shown promising results and include fluorescent in situ hybridization (FISH), direct sequencing, and quantitative polymerase chain reaction (PCR), with similar or higher accuracy and sensitivity than surgical specimens. Preservation and quality of the extracted DNA seem to matter more than the actual number of tumor cells present in the samples. However, major issues still reside in the amount of material, the interference from background non-neoplastic cells, and standardization of parameters for cytological samples.
  
  
  CONCLUSIONS
  This analysis provided evidence that cytological material is suitable for detecting EGFR status using several different methodologies and preparations. New prospective, clinical studies are encouraged for collection and handling of cytological samples as well as for validation of novel techniques in large cohorts.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada. gilda.santos@uhn.on.ca
authors.forename: Gilda
authors.initials: G
authors.lastname: da Cunha Santos
authors.forename: Mauro Ajaj
authors.initials: MA
authors.lastname: Saieg
authors.forename: William
authors.initials: W
authors.lastname: Geddie
authors.forename: Natasha
authors.initials: N
authors.lastname: Leighl
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D003581:Cytodiagnosis / Q000379:methods*; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D018628:Gene Dosage; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D012680:Sensitivity and Specificity
chemical_list: D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors