Epidermal growth factor receptor and insulinlike growth factor 1 receptor expression predict poor survival in pancreatic ductal adenocarcinoma

Cancer. 2012 Jul 15;118(14):3484-93. doi: 10.1002/cncr.26661. Epub 2011 Nov 15.

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.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / mortality
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Female
  • Gene Dosage
  • Gene Expression
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / mortality
  • Prognosis
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism*

Substances

  • Biomarkers, Tumor
  • ErbB Receptors
  • Receptor, IGF Type 1