High eIF4E, VEGF, and microvessel density in stage I to III breast cancer

Ann Surg. 2006 May;243(5):684-90; discussion 691-2. doi: 10.1097/01.sla.0000216770.23642.d8.


Objective: In a prospective trial, to determine if eIF4E overexpression in breast cancer specimens is correlated with VEGF elevation, increased tumor microvessel density (MVD) counts, and a worse clinical outcome irrespective of nodal status.

Summary and background data: In vitro, the overexpression of eukaryotic initiation factor 4E (eIF4E) up-regulates the translation of mRNAs with long 5'-untranslated regions (5'-UTRs). One such gene product is the vascular endothelial growth factor (VEGF).

Methods: A total of 114 stage I to III breast cancer patients were prospectively accrued and followed with a standardized clinical surveillance protocol. Cancer specimens were quantified for eIF4E, VEGF, and MVD. Outcome endpoints were cancer recurrence and cancer-related death.

Results: eIF4E overexpression was found in all cancer specimens (mean +/- SD, 12.5 +/- 7.6-fold). Increasing eIF4E overexpression correlated with increasing VEGF elevation (r = 0.24, P = 0.01, Spearman's coefficient), and increasing MVD counts (r = 0.35, P < 0.0002). Patients whose tumor had high eIF4E overexpression had shorter disease-free survival (P = 0.004, log-rank test) and higher cancer-related deaths (P = 0.002) than patients whose tumors had low eIF4E overexpression. Patients with high eIF4E had a hazard ratio for cancer recurrence and cancer-related death of 1.8 and 2.1 times that of patients with low eIF4E (respectively, P = 0.009 and P = 0.002, Cox proportional hazard model).

Conclusions: In breast cancer patients, increasing eIF4E overexpression in the cancer specimens correlates with higher VEGF levels and MVD counts. Patients whose tumors had high eIF4E overexpression had a worse clinical outcome, independent of nodal status. Thus, eIF4E overexpression in breast cancer appears to predict increased tumor vascularity and perhaps cancer dissemination by hematogenous means.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Breast Neoplasms / blood supply
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Eukaryotic Initiation Factor-4E / analysis
  • Eukaryotic Initiation Factor-4E / biosynthesis*
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Prospective Studies
  • Vascular Endothelial Growth Factor A / analysis
  • Vascular Endothelial Growth Factor A / biosynthesis*


  • Eukaryotic Initiation Factor-4E
  • Vascular Endothelial Growth Factor A