title: Prognostic effect of activated EGFR expression in human colon carcinomas: comparison with EGFR status.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Oncology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Rego
authors.forename: N R
authors.initials: NR
authors.lastname: Foster
authors.forename: T C
authors.initials: TC
authors.lastname: Smyrk
authors.forename: M
authors.initials: M
authors.lastname: Le
authors.forename: M J
authors.initials: MJ
authors.lastname: O'Connell
authors.forename: D J
authors.initials: DJ
authors.lastname: Sargent
authors.forename: H
authors.initials: H
authors.lastname: Windschitl
authors.forename: F A
authors.initials: FA
authors.lastname: Sinicrope
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000368:Aged; D017209:Apoptosis; D002455:Cell Division; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D003131:Combined Modality Therapy; D053843:DNA Mismatch Repair; D018572:Disease-Free Survival; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000032:analysis / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D018773:Genes, erbB-1; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis*; D011379:Prognosis; D040081:Protein Array Analysis; D011499:Protein Processing, Post-Translational; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data
chemical_list: D009363:Neoplasm Proteins; D019000:Phosphotyrosine; C512478:EGFR protein, human; D066246:ErbB Receptors; D005472:Fluorouracil