title: Nuclear EGFR protein expression predicts poor survival in early stage non-small cell lung cancer.
abstract: BACKGROUND
  Nuclear EGFR (nEGFR) has been identified in various human tumor tissues, including cancers of the breast, ovary, oropharynx, and esophagus, and has predicted poor patient outcomes. We sought to determine if protein expression of nEGFR is prognostic in early stage non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Resected stages I and II NSCLC specimens were evaluated for nEGFR protein expression using immunohistochemistry (IHC). Cases with at least one replicate core containing ≥5% of tumor cells demonstrating strong dot-like nucleolar EGFR expression were scored as nEGFR positive.
  
  
  RESULTS
  Twenty-three (26.1% of the population) of 88 resected specimens stained positively for nEGFR. Nuclear EGFR protein expression was associated with higher disease stage (45.5% of stage II vs. 14.5% of stage I; p = 0.023), histology (41.7% in squamous cell carcinoma vs. 17.1% in adenocarcinoma; p = 0.028), shorter progression-free survival (PFS) (median PFS 8.7 months [95% CI 5.1-10.7 mo] for nEGFR positive vs. 14.5 months [95% CI 9.5-17.4 mo] for nEGFR negative; hazard ratio (HR) of 1.89 [95% CI 1.15-3.10]; p = 0.011), and shorter overall survival (OS) (median OS 14.1 months [95% CI 10.3-22.7 mo] for nEGFR positive vs. 23.4 months [95% CI 20.1-29.4 mo] for nEGFR negative; HR of 1.83 [95% CI 1.12-2.99]; p = 0.014).
  
  
  CONCLUSIONS
  Expression of nEGFR protein was associated with higher stage and squamous cell histology, and predicted shorter PFS and OS, in this patient cohort. Nuclear EGFR serves as a useful independent prognostic variable and as a potential therapeutic target in NSCLC.
authors.affiliation: Department of Medicine and Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Traynor
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Weigel
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Oettel
authors.forename: David T
authors.initials: DT
authors.lastname: Yang
authors.forename: Chong
authors.initials: C
authors.lastname: Zhang
authors.forename: Kyungmann
authors.initials: K
authors.lastname: Kim
authors.forename: Ravi
authors.initials: R
authors.lastname: Salgia
authors.forename: Mari
authors.initials: M
authors.lastname: Iida
authors.forename: Toni M
authors.initials: TM
authors.lastname: Brand
authors.forename: Tien
authors.initials: T
authors.lastname: Hoang
authors.forename: Toby C
authors.initials: TC
authors.lastname: Campbell
authors.forename: Hilary R
authors.initials: HR
authors.lastname: Hernan
authors.forename: Deric L
authors.initials: DL
authors.lastname: Wheeler
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002467:Cell Nucleus / Q000378:metabolism; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; C512478:EGFR protein, human; D066246:ErbB Receptors