Impact of epidermal growth factor receptor (EGFR) kinase mutations, EGFR gene amplifications, and KRAS mutations on survival of pancreatic adenocarcinoma

Cancer. 2007 Apr 15;109(8):1561-9. doi: 10.1002/cncr.22559.


Background: Erlotinib, in combination with gemcitabine, has shown clinical benefits in pancreatic adenocarcinoma patients. The presence of EGFR mutations and increased EGFR copy numbers in pancreatic adenocarcinoma was explored.

Methods: Sixty-six pancreatic cancer patients were included in the analysis. The EGFR mutation was analyzed by DNA sequencing of exons 18-21 in the tyrosine kinase domain. KRAS mutation was analyzed by sequencing codons 12, 13, and 61. Quantitative real-time polymerase chain reaction was performed to analyze the copy number of EGFR.

Results: In the current study the EGFR mutation was harbored in only 1 (1.5%) of the 66 inoperable or metastatic pancreatic adenocarcinoma patients. Amino acid substitution was detected in exon 20 of the EGFR gene. Increased EGFR copy numbers (> or =3.0 per cell) were detected in 26 (41%) patients. There was only 1 patient, who had a highly increased EGFR copy number (> or =6.0 per cell), who died, 2.1 months from the date of diagnosis. The EGFR amplification did not significantly influence survival in pancreatic adenocarcinoma patients (P = .935). Thirty-two (49%) of the 65 pancreatic adenocarcinomas examined harbored a point mutation in codons 12 (n = 31) and 61 (n = 1) of the KRAS gene. The presence of a point mutation in codon 12 adversely influenced survival of pancreatic cancer patients (P = .030).

Conclusions: The incidence of somatic mutations in the tyrosine kinase domains of EGFR was very low and the increased gene copy number of EGFR did not significantly influence survival.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality
  • Adult
  • Aged
  • Base Sequence
  • DNA Mutational Analysis
  • ErbB Receptors / genetics*
  • Female
  • Gene Amplification
  • Genes, ras*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / mortality
  • Reverse Transcriptase Polymerase Chain Reaction


  • ErbB Receptors