title: Epidermal growth factor receptor signaling in adenocarcinomas with bronchioloalveolar components.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) has gained importance in non-small cell lung cancer given impressive responses to agents targeting this molecule, particularly in bronchioloalveolar carcinoma (BAC) and adenocarcinomas, mixed subtype, with BAC components (adeno/BAC). This study assesses EGFR signaling in these tumors.
  
  
  METHODS
  One hundred fifty tumors were classified as BAC or adeno/BAC. Tumor marker expression was determined by immunohistochemistry. Correlations with expression were examined for all tumors (BAC and adeno/BAC), and by BAC and adeno/BAC subset analyses.
  
  
  RESULTS
  Positive immunophenotype was observed in 40.6% of tumors for EGFR, 51.3% for p-AKT, 58.7% for p-ERK, and 28.0% for PTEN, with increased overexpression of EGFR (p = 0.025) and p-AKT (p < 0.0001) in adeno/BAC. Epidermal growth factor receptor immunophenotype was greater in never-smokers (p = 0.008) and correlated with improved overall survival (p = 0.018). On subset analysis, EGFR correlated with improved overall survival (p = 0.05) and disease-free interval (p = 0.044) only in adeno/BAC. Epidermal growth factor receptor independently predicted improved disease-free interval in adeno/BAC (p = 0.03; hazard ratio, 0.47; 95% confidence interval, 0.23 to 0.94).
  
  
  CONCLUSIONS
  Overexpression of EGFR in lung adenocarcinomas with components of BAC histology correlate with never-smoker status and improved overall survival and disease-free interval. Epidermal growth factor receptor immunophenotype may be a useful predictor of clinical outcomes in this tumor subset.
authors.affiliation: Laboratory of Epithelial Cancer Biology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: Inderpal S
authors.initials: IS
authors.lastname: Sarkaria
authors.forename: Maureen F
authors.initials: MF
authors.lastname: Zakowski
authors.forename: Duykhanh
authors.initials: D
authors.lastname: Pham
authors.forename: Michael
authors.initials: M
authors.lastname: Hezel
authors.forename: Michael I
authors.initials: MI
authors.lastname: Ebright
authors.forename: Shaokun
authors.initials: S
authors.lastname: Chuai
authors.forename: Ennapadam S
authors.initials: ES
authors.lastname: Venkatraman
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
authors.forename: Valerie W
authors.initials: VW
authors.lastname: Rusch
authors.forename: Bhuvanesh
authors.initials: B
authors.lastname: Singh
mesh_terms: D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011013:Pneumonectomy / Q000379:methods; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D015398:Signal Transduction; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors