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

被引:50
作者
Byrnes, K
White, S
Chu, QY
Meschonat, C
Yu, H
Johnson, LW
DeBenedetti, A
Abreo, F
Turnage, RH
McDonald, JC
Li, BD
机构
[1] Feist Weiller Canc Ctr, Shreveport, LA 71130 USA
[2] Yale Univ, Sch Epidemiol & Publ Hlth, New Haven, CT USA
[3] EA Conway Hosp, Dept Surg, Monroe, LA USA
[4] Louisiana State Univ, Hlth Sci Ctr, Dept Surg, Shreveport, LA 71105 USA
[5] Louisiana State Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Shreveport, LA 71105 USA
[6] Louisiana State Univ, Hlth Sci Ctr, Dept Pathol, Shreveport, LA 71105 USA
关键词
D O I
10.1097/01.sla.0000216770.23642.d8
中图分类号
R61 [外科手术学];
学科分类号
摘要
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.
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页码:684 / 692
页数:9
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