Expression of eukaryotic initiation factor 4E in gastric adenocarcinoma and its association with clinical outcome
Expression of eukaryotic initiation factor 4E in gastric adenocarcinoma and its association with clinical outcome
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DOI：
10.1002/jso.20037
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发表时间：
2004-04-01
影响因子：
2.5
通讯作者：
Chang, KJ
中科院分区：
文献类型：
--
作者：
Chen, CN;Hsieh, FJ;Chang, KJ
背景和目标：eIF 4 E的过表达可导致哺乳动物细胞的致癌转化和不受控制的生长，这可能是通过促进生长控制基因产物的表达而实现的，所述生长控制基因产物通常被抑制。eIF 4 E在人乳腺癌和头颈部鳞状细胞癌中存在过表达，可能对乳腺癌的预后有价值。为了阐明eIF 4 E表达的临床意义，本研究通过定量分析eIF 4 E在人胃癌组织中的表达，并将其与临床病理因素和患者生存率进行相关性研究。相对于来自相同患者的非肿瘤粘膜的对照，表达癌症中eIF 4 E水平的定量。使用免疫组织化学染色确认细胞水平上eIF 4 E的过表达。结果：eIF 4 E在非肿瘤部位的胃腺组织、肠上皮化生和异型增生组织中均有表达，但在胃小凹黏膜中无表达。在69份标本中，平均eIF 4 E表达为5.77 +/- 8.55倍（平均值+/-标准差），范围为0.1倍至38倍。eIF 4 E的表达与肿瘤浸润深度、淋巴结转移、Lauren分型、Borrmann分型及幽门螺杆菌感染无关。eIF 4 E的显著过表达（超过7倍）与肿瘤血管浸润相关（P = 0.046，Fisher精确检验）。eIF 4 E低表达或轻度过表达（< 7倍）患者的生存率显著高于显著过表达（> 7倍）患者（P = 0.01734，logrank检验）。eIF 4 E高表达胃癌患者的预后比低表达者差。它可能作为胃癌预后和治疗的一个额外因素，值得进一步研究。(C)2004 Wiley-Liss，Inc.
Background and Objectives: Overexpression of eIF4E can result in oncogenic transformation and uncontrolled growth of mammalian cells, presumably by facilitating the expression of growth-control gene products, which are normally translationally repressed. Overexpression of eIF4E was present in human breast carcinoma and human head and neck squamous cell carcinoma, and may be of prognostic value in breast carcinomas. In order to elucidate the clinical significance of eIF4E expression, this study was conducted to quantify expression of eIF4E in human gastric cancer tissue and correlate them with clinicopathological factors and patient survival.Methods: Specimens from sixty-nine patients with gastric adenocarcinoma were analyzed and eIF4E overexpression was quantified by Western blot analysis. Quantification of eIF4E levels in cancer was expressed relative to controls from nontumorous mucosa of the same patients. Confirmation of eIF4E overexpression at the cellular level was performed using immunohistochemical staining. The association of clinicopathologic factors and survival with eIF4E expression was analyzed.Results: In non-tumorous parts of specimens, overexpression of eIF4E was always present in gastric glands but not in gastric pits lining mucosa, and it was also expressed in the areas of intestinal metaplasia and dysplasia. In the 69 specimens, the mean eIF4E expression was 5.77 +/- 8.55-fold (mean +/- standard deviation), ranged from from 0.1-fold to 38-fold. The degree of eIF4E expression appeared to be independent of invasion depth of tumor, lymph node metastasis, Lauren classification, Borrmann types, and Helicobacter pylori infection. Marked overexpression of eIF4E (more than seven-fold) was correlated with tumor vascular invasion (P = 0.046, Fisher exact-test). The survival rate of the patients with underexpression or mild overexpression of eIF4E (less than sevenfold) was significantly higher than that with marked eIF4E overexpression (more than sevenfold) (P = 0.01734, log rank test).Conclusions: Marked eIF4E overexpression in gastric cancer was found to be associated with vascular invasion. The prognosis for gastric cancer patients with marked overexpression of eIF4E was worse than those with underexpression. It may serve as an additional prognostic and therapeutic factor in gastric cancer, and deserves further investigation. (C) 2004 Wiley-Liss, Inc.