Pancreatic cancer epidermal growth factor receptor (EGFR) intron 1 polymorphism influences postoperative patient survival and in vitro erlotinib response

Ann Surg Oncol. 2007 Jul;14(7):2150-8. doi: 10.1245/s10434-007-9409-5. Epub 2007 Apr 24.


Background: Epidermal growth factor receptor (EGFR) has a highly polymorphic CA repeat region that affects transcription efficiency and anti-EGFR drug sensitivity in carcinomas. Erlotinib is an EGFR tyrosine kinase inhibitor approved for pancreatic cancer treatment. We analyzed the impact of EGFR intron 1 CA repeat lengths in pancreatic cancer clinical outcome and in vitro response to erlotinib.

Methods: Allele-specific EGFR intron 1 lengths were analyzed in 30 microdissected pancreatic cancer surgical specimens, matched peripheral blood samples, and 9 pancreatic cancer cell lines treated with erlotinib. CA repeat lengths were correlated with survival, tumor parameters, molecular markers of EGFR pathway activation, and in vitro antiproliferative effects of erlotinib.

Results: Both patient samples and cell lines displayed the full spectrum of EGFR CA repeat lengths (14-22 per allele). Patients with shorter sum of total CA repeats (<36) had worse median survival than patients with >or=36 repeats (13.7 vs 30.6 months, P = .002). Shorter patient EGFR intron 1 length correlated with EGFR expression (P = .026). Tumor intron 1 length was identical to that of matched peripheral blood specimens. There was no correlation between EGFR intron 1 length and pancreatic cancer stage, nodal status, grade, or expression of p-EGFR, p-ERK and p-Akt. Shorter EGFR intron 1 length was associated with in vitro response to erlotinib treatment (P = .02).

Conclusions: Shorter EGFR intron 1 CA repeat length is associated with worse pancreatic cancer clinical prognosis and in vitro response to erlotinib. EGFR intron 1 length can be reliably measured in peripheral blood and may translate into a quantitative predictive marker of both pancreatic cancer aggressiveness and erlotinib sensitivity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cell Line, Tumor
  • Erlotinib Hydrochloride
  • Female
  • Genes, erbB-1 / genetics*
  • Humans
  • Introns
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / surgery
  • Polymorphism, Genetic
  • Postoperative Period
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use
  • Quinazolines / therapeutic use
  • Survival Analysis
  • Treatment Outcome


  • Protein Kinase Inhibitors
  • Quinazolines
  • Erlotinib Hydrochloride