EphA2 overexpression correlates with poor prognosis in esophageal squamous cell carcinoma
EphA2 overexpression correlates with poor prognosis in esophageal squamous cell carcinoma
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DOI：
10.1002/ijc.10860
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发表时间：
2003-02-20
影响因子：
6.4
通讯作者：
Kuwano, H
中科院分区：
文献类型：
--
作者：
Miyazaki, T;Kato, H;Kuwano, H
EphA 2是受体酪氨酸激酶的Eph家族的成员，其与称为肝配蛋白的细胞结合配体相互作用。采用免疫组化方法检测80例食管鳞癌（ESCC）患者手术前后EphA 2的表达。EphA 2过表达在80例患者中的40例（50%）中呈阳性。在EphA 2表达与区域淋巴结转移（p=0.023）、淋巴结转移数目（p= 0.011）和肿瘤分化差程度（p=0.004）之间观察到显著相关性。EphA 2阳性患者的生存率低于EphA 2阴性患者（p=0.014）。无EphA 2过表达患者的5年生存率为68%，而EphA 2过表达患者的5年生存率为29%。还在7个ESCC细胞系（TE-1、-2、-8、-13、-15、TT和TTn）和1个永生化人食管角质形成细胞系（CHEK-1）中研究EphA 2表达。Western blotting显示EphA 2在8个细胞系中的表达水平不同。与CHEK-1相比，EphA 2在ESCC细胞系中以高水平表达。在所有细胞系中证实了EphA 2磷酸化。北方印迹分析显示，EphA 2 mRNA在TE-1细胞中的表达高于其它ESCC细胞系。在ESCC细胞系的Western印迹分析上观察到的小缺口表明，在翻译点处可能存在EphA 2调节的机制。总之，EphA 2过表达似乎与ESCC中肿瘤分化程度差和淋巴结转移有关。因此，具有EphA 2过表达的患者比没有EphA 2过表达的患者具有更差的预后：EphA 2是防止ESCC细胞扩散到淋巴引流中的潜在靶点。(C)2002 Wiley-Liss，Inc.
EphA2 is a member of the Eph family of receptor tyrosine kinases, which interact with cell-bound ligands known as ephrins. EphA2 expression was investigated by immunohistochemistry with an anti-EphA2 monoclonal antibody in 80 patients with esophageal squamous cell carcinoma (ESCC) who had undergone surgery. EphA2 overexpression was positive in 40 of the 80 patients (50%). A significant correlation was observed between EphA2 expression and regional lymph node metastasis (p=0.023), number of lymph node metastases (p=0.01 1) and poor degree of tumor differentiation (p=0.004). The survival rates of EphA2-positive patients were poorer than those of EphA2-negative patients (p=0.014). The 5-year survival rate of patients without EphA2 overexpression was 68%, whereas that of patients with EphA2 overexpression was 29%. EphA2 expression was also investigated in 7 ESCC cell lines (TE-1, -2, -8, -13, -15, TT and TTn) and I immortalized human esophageal keratinocyte cell line (CHEK-1). Western blotting revealed different levels of EphA2 expression in the 8 cell lines. EphA2 was expressed at a high level in the ESCC cell lines compared to CHEK-1. EphA2 phosphorylation was demonstrated in all cell lines. Northern blot analysis showed that EphA2 mRNA expression in TE-1 was greater than that in the other ESCC cell lines. The observation of small gaps on Western blot analysis of the ESCC cell lines suggests that there may be a mechanism for EphA2 regulation at the point of translation. In conclusion, EphA2 overexpression appears to be related to poor degree of tumor differentiation and lymph node metastasis in ESCC. Consequently, patients with EphA2 overexpression have a poorer prognosis than those without : EphA2 is a potential target to prevent ESCC cells spreading into the lymphatic drainage. (C) 2002 Wiley-Liss, Inc.