title: PTEN and PIK3CA gene copy numbers and poor outcomes in non-small cell lung cancer patients with gefitinib therapy.
abstract: METHODS
  Fluorescent in situ hybridisation analyses of PTEN, PIK3CA, EGFR and CEN7 were performed on tumour specimens from patients treated on the expanded access gefitinib trial. Progression-free survival (PFS) and overall survival (OS) were correlated with outcomes in all patients and EGFR wild-type patients.
  
  
  RESULTS
  Progression-free survival (hazard ratio=2.54, P<0.001) and OS (hazard ratio=4.04, P<0.001) were significantly shorter in patients whose tumours had all of the following molecular patterns: CEN7 <4 copies per cell, PTEN loss (<2 copies in at least 20% of cells), and PIK3CA gain (>2 copies in at least 40% of cells) both in all and EGFR wild-type only patients.
  
  
  CONCLUSIONS
  The combination of low CEN7 copy number, PTEN loss, and PI3KCA gain may be useful for identifying NSCLC patients unlikely to benefit from treatment with EGFR (TKIs), specifically in wild-type EGFR cases.
authors.affiliation: Section of Medical Oncology, Rush University Medical Center, 1725 West Harrison Street 821, Chicago, IL 60612, USA. mary_fidler@rush.edu
authors.forename: M J
authors.initials: MJ
authors.lastname: Fidler
authors.forename: L E
authors.initials: LE
authors.lastname: Morrison
authors.forename: S
authors.initials: S
authors.lastname: Basu
authors.forename: L
authors.initials: L
authors.lastname: Buckingham
authors.forename: K
authors.initials: K
authors.lastname: Walters
authors.forename: M
authors.initials: M
authors.lastname: Batus
authors.forename: K K
authors.initials: KK
authors.lastname: Jacobson
authors.forename: S S
authors.initials: SS
authors.lastname: Jewell
authors.forename: J
authors.initials: J
authors.lastname: Coon
authors.forename: P D
authors.initials: PD
authors.lastname: Bonomi
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D058534:Class I Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D018628:Gene Dosage; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011799:Quinazolines / Q000627:therapeutic use*; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D000077156:Gefitinib
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