title: Epidermal growth factor receptor and insulinlike growth factor 1 receptor expression predict poor survival in pancreatic ductal adenocarcinoma.
abstract: BACKGROUND
  The aim of this study was to evaluate the expression of epidermal growth factor receptor (EGFR) and insulinlike growth factor 1 receptor (IGF-1R) proteins and IGF-1R gene copy numbers in pancreatic ductal adenocarcinoma in relation to patients' characteristics and prognosis.
  
  
  METHODS
  Immunohistochemical staining was performed on formalin-fixed paraffin-embedded tissue derived from tumor specimens recovered during surgery. Slides were evaluated for membranous EGFR and IGF-1R staining using both the HercepTest and the semiquantitative H-score systems. Chromogenic in situ hybridization was performed to quantify IGF-1R gene copy number. The primary outcome was the association between EGFR expression, IGF-1R expression-in both neoplastic epithelial and stromal cells-or IGF-1R gene copy number and overall survival. Secondary outcomes included associations between EFGR and IGF-1R expression and pathologic variables.
  
  
  RESULTS
  A total of 105 patients were included. EGFR expression was present in 30.4% of cases and was associated with lymph node metastasis (P = .038). IGF-1R was overexpressed in 53% of tumors and correlated with higher tumor grade (P = .033). High membranous expression of EGFR (P < .001) and/or IGF-1R (P = .004), the cytoplasmic detection of EGFR (P = .027), and high expression levels of IGF-1R in the tumoral stroma (P < .001) were all associated with shorter overall survival, being significantly better in patients who simultaneously do not express membranous EGFR or stromal IGF-1R.
  
  
  CONCLUSIONS
  EGFR and IGF-1R expression, in neoplastic and stromal cells, seems to be an important prognostic factor.
authors.affiliation: Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA, USA. Matias.Valsecchi@jeffersonhospital.org
authors.forename: Matias E
authors.initials: ME
authors.lastname: Valsecchi
authors.forename: Mary
authors.initials: M
authors.lastname: McDonald
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Brody
authors.forename: Terry
authors.initials: T
authors.lastname: Hyslop
authors.forename: Boris
authors.initials: B
authors.lastname: Freydin
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Yeo
authors.forename: Charalambos
authors.initials: C
authors.lastname: Solomides
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Peiper
authors.forename: Agnieszka K
authors.initials: AK
authors.lastname: Witkiewicz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000401:mortality; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018628:Gene Dosage; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1