Byrnes Kerry, White Stephen, Chu Quyen, Meschonat Carol, Yu Herbert, Johnson Lester W, Debenedetti Arrigo, Abreo Fleurette, Turnage Richard H, McDonald John C, Li Benjamin D
Department of Surgery, Louisiana State University Health Sciences Center in Shreveport, 71130, USA.
Ann Surg. 2006 May;243(5):684-90; discussion 691-2. doi: 10.1097/01.sla.0000216770.23642.d8.
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.
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).
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.
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).
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.
在一项前瞻性试验中，确定乳腺癌标本中真核生物起始因子4E（eIF4E）过表达是否与血管内皮生长因子（VEGF）升高、肿瘤微血管密度（MVD）计数增加以及无论淋巴结状态如何均更差的临床结局相关。
在体外，真核生物起始因子4E（eIF4E）的过表达上调具有长5'非翻译区（5'-UTR）的mRNA的翻译。一种这样的基因产物是血管内皮生长因子（VEGF）。
前瞻性纳入114例I至III期乳腺癌患者，并采用标准化临床监测方案进行随访。对癌组织标本进行eIF4E、VEGF和MVD定量分析。结局终点为癌症复发和癌症相关死亡。
在所有癌组织标本中均发现eIF4E过表达（平均值±标准差，12.5±7.6倍）。eIF4E过表达增加与VEGF升高增加相关（r = 0.24，P = 0.01，Spearman系数），以及MVD计数增加相关（r = 0.35，P < 0.0002）。肿瘤eIF4E过表达高的患者与肿瘤eIF4E过表达低的患者相比，无病生存期更短（P = 0.004，对数秩检验），癌症相关死亡更高（P = 0.002）。eIF4E高表达患者癌症复发和癌症相关死亡的风险比分别是eIF4E低表达患者的1.8倍和2.1倍（分别为P = 0.009和P = 0.002，Cox比例风险模型）。
在乳腺癌患者中，癌组织标本中eIF4E过表达增加与更高的VEGF水平和MVD计数相关。肿瘤eIF4E过表达高的患者临床结局更差，与淋巴结状态无关。因此，乳腺癌中eIF4E过表达似乎预示肿瘤血管生成增加，可能通过血行途径导致癌症播散。
