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


BACKGROUND
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.
Byrnes
Kerry
K
Department of Surgery, Louisiana State University Health Sciences Center in Shreveport, 71130, USA.
White
Stephen
S
Chu
Quyen
Q
Meschonat
Carol
C
Yu
Herbert
H
Johnson
Lester W
LW
Debenedetti
Arrigo
A
Abreo
Fleurette
F
Turnage
Richard H
RH
McDonald
John C
JC
Li
Benjamin D
BD
D001943:Breast Neoplasms / Q000098:blood supply / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D039561:Eukaryotic Initiation Factor-4E / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000096:biosynthesis*
D039561:Eukaryotic Initiation Factor-4E; D042461:Vascular Endothelial Growth Factor A