Comparative analysis of the EGF-receptor family in pancreatic cancer: expression of HER-4 correlates with a favourable tumor stage

Int J Surg Investig. 2001;2(5):393-400.


Background: Of major interest for a better molecular understanding of pancreatic cancer is the EGF receptor family. While HER-1 (EGF-receptor) and HER-2 have been extensively studied, little is known about the clinical significance of HER-3 and especially HER-4 expression.

Methods: We investigated the expression of HER-1, HER-2, HER-3 and HER-4 in 11 pancreatic cancer cell lines using FACS-analysis and determined expression and overexpression of these receptors in 24 pancreatic cancer specimens. Therefore, we used two different immunostaining techniques: a highly sensitive streptavidin-biotin method showed receptor expression while an approximatly 10-fold less sensitive indirect immunperoxidase technique determined receptor-overexpression.

Results: HER-1 and HER-2 were expressed by all 11 pancreatic cancer cell lines, HER-3 was found in 82% and HER-4 in 54% of the cell lines. Low levels of HER-1, HER-2 and HER-3 were detected in all tumor samples but overexpression was only found in 33%, 25% and 50% of the cases, respectively. HER-4 was expressed by 37% of the tumor specimens but overexpression was seen in one patient only. HER-1 and HER-2 overexpression increased in parallel with the tumor stage and R0-resected tumors showed significantly less often overexpression compared to R1/R2 resected tumors (p < 0.05). In contrast, 54% of the R0-resected vs. 18% of the R1/R2 resected tumors showed HER-4 expression (p = 0.07) and HER-4 was exclusively found in non-metastatic tumors (p = 0.0149).

Conclusion: Our data indicate that HER-1 and HER-2 overexpression contributes to a more aggressive phenotype. In contrast, the lack of HER-4 expression might increase the metastatic capacity of pancreatic cancer cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / analysis*
  • ErbB Receptors / analysis
  • ErbB Receptors / genetics*
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Gene Amplification
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Male
  • Neoplasm Staging
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology*
  • Probability
  • Prognosis
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-3 / genetics
  • Receptor, ErbB-4
  • Sampling Studies
  • Sensitivity and Specificity
  • Tumor Cells, Cultured


  • Biomarkers, Tumor
  • ERBB4 protein, human
  • ErbB Receptors
  • Receptor, ErbB-2
  • Receptor, ErbB-3
  • Receptor, ErbB-4