title: High coexpression of both EGFR and IGF1R correlates with poor patient prognosis in resected non-small-cell lung cancer.
abstract: BACKGROUND
  Recent experimental and biomarker evidence indicates that the epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor 1 (IGF1R) interact in the pathogenesis of malignant epithelial tumors, including lung cancer. This study examines the expression of both receptors and their prognostic significance in surgically resected non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  EGFR and IGF1R expression were evaluated in 184 patients with NSCLC (83 squamous cell carcinomas [SCCs], 83 adenocarcinomas [ADCs], and 18 other types) using immunohistochemical (IHC) analysis. Expression of both receptors was examined in matched fresh frozen normal and tumor tissues from 40 patients with NSCLC (20 SCCs and 20 ADCs) by Western blot analysis.
  
  
  RESULTS
  High EGFR expression was detected in 51% of patients, and SCCs had higher EGFR expression than did non-SCCs (57.4% vs. 42.5%; P = .028). High IGF1R expression was observed in 53.8% of patients, with SCC having higher expression than non-SCC (62.6% vs. 37.3%; P = .0004). A significant association was shown between EGFR and IGF1R protein overexpression (P < .005). Patients with high expression of both receptors had a poorer overall survival (OS) (P = .04). Higher EGFR and IGF1R expression was detected in resected tumors relative to matched normal tissues (P = .0004 and P = .0009), with SCC having higher expression levels than ADC.
  
  
  CONCLUSIONS
  Our findings indicate a close interrelationship between EGFR and IGF1R. Coexpression of both receptors correlates with poor survival. This subset of patients may benefit from treatments cotargeting EGFR and IGF1R.
authors.affiliation: Thoracic Oncology Research Group, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin, Ireland. Electronic address: kgately@stjames.ie.
authors.forename: Kathy
authors.initials: K
authors.lastname: Gately
authors.affiliation: Thoracic Oncology Research Group, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin, Ireland.
authors.forename: Lydia
authors.initials: L
authors.lastname: Forde
authors.affiliation: Thoracic Oncology Research Group, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin, Ireland.
authors.forename: Sinead
authors.initials: S
authors.lastname: Cuffe
authors.affiliation: Department of Pathology, Beaumont Hospital and the Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Robert
authors.initials: R
authors.lastname: Cummins
authors.affiliation: Department of Pathology, Beaumont Hospital and the Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Elaine W
authors.initials: EW
authors.lastname: Kay
authors.affiliation: Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Feuerhake
authors.affiliation: Thoracic Oncology Research Group, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin, Ireland.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: O'Byrne
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D018287:Carcinoma, Large Cell / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D009367:Neoplasm Staging; D011379:Prognosis; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C512478:EGFR protein, human; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1
keywords: EGFR; IGF1R; NSCLC; Prognostic marker