title: Epidermal growth factor receptor (EGFR) mutations are exceptionally rare in thyroid transcription factor (TTF-1)-negative adenocarcinomas of the lung.
abstract: BACKGROUND
  Approximately 70% of lung adenocarcinomas express TTF-1. EGFR mutations are present in 13-15% of Western adenocarcinoma patients. This paper investigates TTF1 as a negative predictor of mutant EGFR in lung adenocarcinomas.
  
  
  RESULTS
  In the pilot cohort (N = 301) two of 224 specimens positive for EGFR mutations had negative TTF-1 expression (sensitivity 99.1%, 95% confidence interval (CI) 96.8-99.9%). Estimated negative predictive values (NPV) for EGFR mutation prevalence rates of 13% and 15% are 99.5% (95% credible interval (CRI) 98.6%-99.9%) and 99.4% (CRI - 98.4%-99.9%). For EGFR mutation rates of 13% and 15%, using validation cohort data (211 patients), the estimated NPVs were 97% (95% CRI 92%-99%) and 96% (95% CRI 91%-99%).
  
  
  METHODS
  Formalin-fixed paraffin-embedded tumors from lung adenocarcinoma patients were analyzed for EGFR mutations by allele-specific PCR in the 'pilot cohort'. TTF-1 status was documented as positive or negative. Negative predictive value (NPV) for a range of true prevalence of EGFR mutation (1%-50%) was estimated using Bayesian modeling. The hypothesis was validated in a separate 'validation' cohort using the same modeling.
  
  
  CONCLUSIONS
  An overwhelming majority of TTF-1 negative adenocarcinomas will be negative for EGFR mutations. This finding allows for earlier initiation of chemotherapy in newly diagnosed TTF-1 negative adenocarcinomas of the lung with stage IV disease.
authors.affiliation: MD Anderson Cancer Center, Houston TX 77004.
authors.forename: Neeta
authors.initials: N
authors.lastname: Somaiah
authors.affiliation: Rush University Medical Center, Chicago, IL 60612.
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Fidler
authors.affiliation: Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Garrett-Mayer
authors.affiliation: Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425.
authors.forename: Amy
authors.initials: A
authors.lastname: Wahlquist
authors.affiliation: Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Shirai
authors.affiliation: Rush University Medical Center, Chicago, IL 60612.
authors.forename: Lela
authors.initials: L
authors.lastname: Buckingham
authors.affiliation: North Shore University Health Systems/University of Chicago, Evanston, IL 60201.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hensing
authors.affiliation: Rush University Medical Center, Chicago, IL 60612.
authors.forename: Philip
authors.initials: P
authors.lastname: Bonomi
authors.affiliation: MD Anderson Cancer Center, Houston TX 77004.
authors.forename: George R
authors.initials: GR
authors.lastname: Simon
keywords: EGFR; NSCLC; TTF-1; adenocarcinoma