High eIF4E, VEGF, and microvessel density in stage I to III breast cancer
High eIF4E, VEGF, and microvessel density in stage I to III breast cancer
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DOI：
10.1097/01.sla.0000216770.23642.d8
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发表时间：
2006-05-01
影响因子：
9
通讯作者：
Li, BD
中科院分区：
文献类型：
--
作者：
Byrnes, K;White, S;Li, BD
目的：在一项前瞻性试验中，确定乳腺癌标本中eIF4E过表达是否与VEGF升高、肿瘤微血管密度（MVD）计数增加以及与淋巴结状态无关的较差临床结果相关。摘要与背景数据：在体外，真核起始因子4E （eIF4E）的过表达上调具有长5'-非翻译区（5'- utr）的mrna的翻译。其中一个基因产物就是血管内皮生长因子（VEGF）。方法：对114例I至III期乳腺癌患者进行前瞻性统计，并采用标准化的临床监测方案进行随访。肿瘤标本定量检测eIF4E、VEGF和MVD。结局终点为癌症复发和癌症相关死亡。结果：eIF4E在所有肿瘤标本中均过表达（平均+/- SD， 12.5 +/- 7.6倍）。eIF4E过表达增加与VEGF升高（r = 0.24, P = 0.01， Spearman系数）和MVD计数增加相关（r = 0.35, P < 0.0002）。eIF4E高表达肿瘤患者的无病生存期（P = 0.004， log-rank检验）较eIF4E低表达肿瘤患者短，肿瘤相关死亡率（P = 0.002）较高。高eIF4E患者癌症复发和癌症相关死亡的风险比是低eIF4E患者的1.8倍和2.1倍（Cox比例风险模型，P = 0.009和P = 0.002）。结论：在乳腺癌患者中，肿瘤标本中eIF4E过表达的增加与VEGF水平和MVD计数升高相关。肿瘤中eIF4E高表达的患者临床预后较差，与淋巴结状态无关。因此，乳腺癌中eIF4E的过表达似乎预示着肿瘤血管的增加和可能通过血液途径的癌症传播。
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.