Medical Oncology

, Volume 29, Issue 1, pp 134–139 | Cite as

Cell membrane and cytoplasmic epidermal growth factor receptor expression in pancreatic ductal adenocarcinoma

  • Amit Mahipal
  • Mary J. Mcdonald
  • Agnieszka Witkiewicz
  • Brian I. CarrEmail author
Original Paper


The significance of over-expression of epidermal growth factor receptor (EGFR) in pancreatic carcinoma is unclear. In this study, we examined the association between EGFR over-expression (membranous and cytoplasmic), the associated histopathologic features and clinical outcomes in post-resection pancreatic cancer patients. EGFR expression was determined immunohistochemically in 90 patients who underwent resection for pancreatic cancer. Cytoplasmic expression was considered positive if EGFR expression was seen in the cytoplasm in ≥10% of cells. Cell membrane staining was scored from 0 to 3+, with 2+ and 3+ being considered as membrane over-expression. Overall survival and progression-free survival were calculated using the Kaplan–Meier method, and survival curves were compared by the log-rank test. Out of 90 patients, 51 (57%) and 74 (68%) patients had membrane and cytoplasmic EGFR over-expression, respectively. There was a statistically significant correlation between cell membrane EGFR over-expression and lymph node positivity (P = 0.03). Patients with membrane EGFR over-expression had a shorter median progression-free survival (10.7 vs. 17.0 months, P = 0.02) and overall survival (15.9 months vs. 25.3 months, P = 0.17). Cytoplasmic EFGR over-expression was not significantly associated with recurrence or survival. Membrane EGFR over-expression in resected pancreatic cancer patients was associated with worse clinical outcomes than non-over-expression.


EGF receptor Pancreatic cancer Invasion Recurrence Prognosis 


  1. 1.
    Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.PubMedCrossRefGoogle Scholar
  2. 2.
    Lemoine NR, et al. The epidermal growth factor receptor in human pancreatic cancer. J Pathol. 1992;166:7–12.PubMedCrossRefGoogle Scholar
  3. 3.
    Nicholson RI, Gee JM, Harper ME. EGFR and cancer prognosis. Eur J Cancer. 2001;37(Suppl 4):S9–15.PubMedCrossRefGoogle Scholar
  4. 4.
    Kopp R, et al. Clinical implications of the EGF receptor/ligand system for tumor progression and survival in gastrointestinal carcinomas: evidence for new therapeutic options. Recent Results Cancer Res. 2003;162:115–32.PubMedCrossRefGoogle Scholar
  5. 5.
    Faller BA, Burtness B. Treatment of pancreatic cancer with epidermal growth factor receptor-targeted therapy. Biologics. 2009;3:419–28.PubMedGoogle Scholar
  6. 6.
    Yamanaka Y. The immunohistochemical expressions of epidermal growth factors, epidermal growth factor receptors and c-erbB-2 oncoprotein in human pancreatic cancer. Nippon Ika Daigaku Zasshi. 1992;59:51–61.PubMedGoogle Scholar
  7. 7.
    Yamanaka Y, et al. Coexpression of epidermal growth factor receptor and ligands in human pancreatic cancer is associated with enhanced tumor aggressiveness. Anticancer Res. 1993;13:565–9.PubMedGoogle Scholar
  8. 8.
    Dong M, et al. Epidermal growth factor and its receptor as prognostic indicators in Chinese patients with pancreatic cancer. Anticancer Res. 1998;18:4613–9.PubMedGoogle Scholar
  9. 9.
    Uegaki K, et al. Clinicopathological significance of epidermal growth factor and its receptor in human pancreatic cancer. Anticancer Res. 1997;17:3841–7.PubMedGoogle Scholar
  10. 10.
    Gansauge F, Gansauge S, Muller J, Schmid E, Beger HG. Prognostic value of molecular biology and immunologic parameters in human pancreatic carcinoma. Langenbecks Arch Chir Suppl Kongressbd. 1998;115:69–72.PubMedGoogle Scholar
  11. 11.
    Kuniyasu H, Abbruzzese JL, Cleary KR, Fidler IJ. Induction of ductal and stromal hyperplasia by basic fibroblast growth factor produced by human pancreatic carcinoma. Int J Oncol. 2001;19:681–5.PubMedGoogle Scholar
  12. 12.
    Tobita K, et al. Epidermal growth factor receptor expression in human pancreatic cancer: significance for liver metastasis. Int J Mol Med. 2003;11:305–9.PubMedGoogle Scholar
  13. 13.
    Ueda S, et al. The correlation between cytoplasmic overexpression of epidermal growth factor receptor and tumor aggressiveness: poor prognosis in patients with pancreatic ductal adenocarcinoma. Pancreas. 2004;29:e1–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Bloomston M, Bhardwaj A, Ellison EC, Frankel WL. Epidermal growth factor receptor expression in pancreatic carcinoma using tissue microarray technique. Dig Surg. 2006;23:74–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Takikita M, et al. Associations between selected biomarkers and prognosis in a population-based pancreatic cancer tissue microarray. Cancer Res. 2009;69:2950–5.PubMedCrossRefGoogle Scholar
  16. 16.
    Zhang L, Yuan SZ. Expression of c-erbB-2 oncogene protein, epidermal growth factor receptor, and TGF-beta1 in human pancreatic ductal adenocarcinoma. Hepatobiliary Pancreat Dis Int. 2002;1:620–3.PubMedGoogle Scholar
  17. 17.
    Piyathilake CJ, et al. Differential expression of growth factors in squamous cell carcinoma and precancerous lesions of the lung. Clin Cancer Res. 2002;8:734–44.PubMedGoogle Scholar
  18. 18.
    Akslen LA, Myking AO, Salvesen H, Varhaug JE. Prognostic impact of EGF-receptor in papillary thyroid carcinoma. Br J Cancer. 1993;68:808–12.PubMedCrossRefGoogle Scholar
  19. 19.
    Bruns CJ, et al. Blockade of the epidermal growth factor receptor signaling by a novel tyrosine kinase inhibitor leads to apoptosis of endothelial cells and therapy of human pancreatic carcinoma. Cancer Res. 2000;60:2926–35.PubMedGoogle Scholar
  20. 20.
    Ng SS, Tsao MS, Nicklee T, Hedley DW. Effects of the epidermal growth factor receptor inhibitor OSI-774, Tarceva, on downstream signaling pathways and apoptosis in human pancreatic adenocarcinoma. Mol Cancer Ther. 2002;1:777–83.PubMedGoogle Scholar
  21. 21.
    Moore MJ, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25:1960–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Xiong HQ, et al. Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, in combination with gemcitabine for advanced pancreatic cancer: a multicenter phase II trial. J Clin Oncol. 2004;22:2610–6.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Amit Mahipal
    • 1
  • Mary J. Mcdonald
    • 2
  • Agnieszka Witkiewicz
    • 2
  • Brian I. Carr
    • 1
    Email author
  1. 1.Department of Medical OncologyThomas Jefferson UniversityPhiladelphiaUSA
  2. 2.Department of PathologyThomas Jefferson UniversityPhiladelphiaUSA

Personalised recommendations