Prognostic effect of activated EGFR expression in human colon carcinomas: comparison with EGFR status

Br J Cancer. 2010 Jan 5;102(1):165-72. doi: 10.1038/sj.bjc.6605473. Epub 2009 Dec 8.


Background: Evidence suggests that epidermal growth factor receptor (EGFR)-activation status may better predict the clinical behaviour of colon cancers than does EGFR expression. However, the prognostic effect of phospho-EGFR in primary colon cancer remains undefined.

Methods: Phospho-EGFR (Tyr-1173) and EGFR expression were analysed by immunohistochemistry (IHC) in tissue microarrays of TNM stage II and III colon cancers from completed adjuvant therapy trials (n=388). Staining intensity was scored and correlated with clinicopathological variables, DNA mismatch repair (MMR) status, rates of cell proliferation (Ki-67), apoptosis (caspase-3), and patient survival.

Results: Phospho-EGFR expression was detected in 157 of 388 (40%) tumours, whereas EGFR was found in 214 of 361 (59%). Although phospho-EGFR was unrelated to clinicopathological variables, strong EGFR intensity was associated with higher tumour stage (P=0.03). Tumours overexpressing EGFR (P=0.0002) or phospho-EGFR (P=0.015) showed increased Ki-67, but not caspase-3 expression. Phospho-EGFR was not prognostic. EGFR intensity was associated with worse disease-free survival (DFS) (hazard ratio (HR): 1.21 (1.03, 1.41); P=0.019) and overall survival (OS) (HR: 1.19 (1.02, 1.39); P=0.028). Tumours expressing both EGFR and phospho-EGFR had similar survival as EGFR alone. Stage and lymph node number were prognostic for DFS and OS, and histological grade for OS. EGFR was an independent predictor of DFS (P=0.042) after adjustment for stage, histological grade, age, and MMR status.

Conclusion: Phospho-EGFR and EGFR expression were associated with tumour cell hyperproliferation. Phospho-EGFR was not prognostic, whereas increased EGFR intensity was independently associated with poor DFS.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Aged
  • Apoptosis
  • Cell Division
  • Chemotherapy, Adjuvant
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / enzymology*
  • Colonic Neoplasms / mortality
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / surgery
  • Combined Modality Therapy
  • DNA Mismatch Repair
  • Disease-Free Survival
  • Enzyme Activation
  • ErbB Receptors / analysis
  • ErbB Receptors / metabolism*
  • Female
  • Fluorouracil / administration & dosage
  • Follow-Up Studies
  • Genes, erbB-1
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Phosphorylation
  • Phosphotyrosine / analysis*
  • Prognosis
  • Protein Array Analysis
  • Protein Processing, Post-Translational*
  • Randomized Controlled Trials as Topic / statistics & numerical data


  • Neoplasm Proteins
  • Phosphotyrosine
  • EGFR protein, human
  • ErbB Receptors
  • Fluorouracil