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EphA2和E-钙黏蛋白在结直肠癌中的表达:与癌症转移的相关性

Expression of EphA2 and E-cadherin in colorectal cancer: correlation with cancer metastasis.

作者信息

Saito Tetsuya, Masuda Norihiro, Miyazaki Tatsuya, Kanoh Kenichi, Suzuki Hideki, Shimura Tatsuo, Asao Takayuki, Kuwano Hiroyuki

机构信息

Department of General Surgical Science (Surgery I), Gunma University, Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.

出版信息

Oncol Rep. 2004 Mar;11(3):605-11.

Abstract

Recently, overexpression of EphA2, a member of the Eph family of receptor tyrosine kinases, has been reported in several cancers. Reduced expression of E-cadherin, an intercellular adhesion molecule of epithelial cells, has been reported to be associated with aggressive clinicopathological phenotypes in various cancers. In epithelial cells, EphA2 and E-cadherin co-localize to sites of cell-cell contact, and it has been shown that E-cadherin regulates EphA2. This study aimed to clarify the relationship between the expression of the EphA2 and E-cadherin proteins and clinicopathological characteristics, with reference to the expression levels of both EphA2 and E-cadherin, in patients with colorectal cancer. We performed immunohistochemical staining of EphA2 and E-cadherin with EphA2 and E-cadherin monoclonal antibodies in samples from 194 primary lesions of colorectal cancer. The expression level of EphA2 had a statistically significant relationship with liver metastasis, lymphatic vessel invasion and clinical stage (p=0.0477, 0.0316 and 0.0467, respectively). In addition, the positivity rate of EphA2 was significantly higher in primary lesions with lymph node metastasis than in those without metastasis (p=0.0014). However, the expression level of E-cadherin had an inverse relationship with both differentiation level of the tumor and lymphatic vessel invasion (p=0.0430 and 0.0320, respectively). Furthermore, a significant relationship between the expression of EphA2 and E-cadherin was observed. In conclusion, our study revealed that the overexpression of EphA2 protein in colorectal carcinoma tissue correlates closely with cancer progression and hematogenous and lymphogenous metastasis, suggesting that both EphA2 and E-cadherin may play an important role in tumor metastasis in colorectal cancer.

摘要

最近,有报道称受体酪氨酸激酶Eph家族成员EphA2在多种癌症中过表达。上皮细胞间黏附分子E-钙黏蛋白的表达降低与多种癌症侵袭性的临床病理表型相关。在上皮细胞中,EphA2和E-钙黏蛋白共定位于细胞间接触位点,并且已表明E-钙黏蛋白可调节EphA2。本研究旨在参考EphA2和E-钙黏蛋白的表达水平,阐明EphA2和E-钙黏蛋白蛋白表达与结直肠癌患者临床病理特征之间的关系。我们用EphA2和E-钙黏蛋白单克隆抗体对194例结直肠癌原发灶样本进行了EphA2和E-钙黏蛋白的免疫组化染色。EphA2的表达水平与肝转移、淋巴管侵犯和临床分期具有统计学意义的相关性(分别为p=0.0477、0.0316和0.0467)。此外,有淋巴结转移的原发灶中EphA2的阳性率显著高于无转移的原发灶(p=0.0014)。然而,E-钙黏蛋白的表达水平与肿瘤分化程度和淋巴管侵犯均呈负相关(分别为p=0.0430和0.0320)。此外,还观察到EphA2和E-钙黏蛋白表达之间存在显著相关性。总之,我们的研究表明,结直肠癌组织中EphA2蛋白的过表达与癌症进展以及血行和淋巴转移密切相关,提示EphA2和E-钙黏蛋白在结直肠癌肿瘤转移中可能都起重要作用。

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