title: EGFR mutation testing in lung cancer: a review of available methods and their use for analysis of tumour tissue and cytology samples.
abstract: OBJECTIVE
  Activating mutations in the gene encoding epidermal growth factor receptor (EGFR) can confer sensitivity to EGFR tyrosine kinase inhibitors such as gefitinib in patients with advanced non-small-cell lung cancer. Testing for mutations in EGFR is therefore an important step in the treatment-decision pathway. We reviewed reported methods for EGFR mutation testing in patients with lung cancer, initially focusing on studies involving standard tumour tissue samples. We also evaluated data on the use of cytology samples in order to determine their suitability for EGFR mutation analysis.
  
  
  METHODS
  We searched the MEDLINE database for studies reporting on EGFR mutation testing methods in patients with lung cancer.
  
  
  RESULTS
  Various methods have been investigated as potential alternatives to the historical standard for EGFR mutation testing, direct DNA sequencing. Many of these are targeted methods that specifically detect the most common EGFR mutations. The development of targeted mutation testing methods and commercially available test kits has enabled sensitive, rapid and robust analysis of clinical samples. The use of screening methods, subsequent to sample micro dissection, has also ensured that identification of more rare, uncommon mutations is now feasible. Cytology samples including fine needle aspirate and pleural effusion can be used successfully to determine EGFR mutation status provided that sensitive testing methods are employed.
  
  
  CONCLUSIONS
  Several different testing methods offer a more sensitive alternative to direct sequencing for the detection of common EGFR mutations. Evidence published to date suggests cytology samples are viable alternatives for mutation testing when tumour tissue samples are not available.
authors.affiliation: AstraZeneca, Macclesfield, Alderley Park, UK. gillian.ellison@astrazeneca.com
authors.forename: Gillian
authors.initials: G
authors.lastname: Ellison
authors.forename: Guanshan
authors.initials: G
authors.lastname: Zhu
authors.forename: Alexandros
authors.initials: A
authors.lastname: Moulis
authors.forename: Simon
authors.initials: S
authors.lastname: Dearden
authors.forename: Georgina
authors.initials: G
authors.lastname: Speake
authors.forename: Rose
authors.initials: R
authors.lastname: McCormack
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001707:Biopsy, Needle; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D003581:Cytodiagnosis; D004252:DNA Mutational Analysis / Q000295:instrumentation / Q000379:methods; D066246:ErbB Receptors / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D042282:Microdissection; D009154:Mutation; D018579:Patient Selection; D010996:Pleural Effusion / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D057285:Precision Medicine; D011237:Predictive Value of Tests; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011933:Reagent Kits, Diagnostic; D012680:Sensitivity and Specificity; D013048:Specimen Handling / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011933:Reagent Kits, Diagnostic; C512478:EGFR protein, human; D066246:ErbB Receptors