Overexpression of ephrinB2 and EphB4 in tumor advancement of uterine endometrial cancers
Overexpression of ephrinB2 and EphB4 in tumor advancement of uterine endometrial cancers
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DOI：
10.1093/annonc/mdl414
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发表时间：
2007-03-01
影响因子：
50.5
通讯作者：
Tamaya, T.
中科院分区：
文献类型：
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作者：
Alam, S. M.;Fujimoto, J.;Tamaya, T.
背景：配体ephrinB2及其受体EphB4参与人类多种肿瘤的生长。这促使我们研究ephrinB2和EphB4在子宫内膜癌中的表达和定位，分析ephrinB2/EphB4在临床中的功能。材料和方法：采用免疫组织化学和实时RT-PCR方法分别测定68例子宫内膜癌和16例正常子宫内膜组织中ephrinB2和EphB4的组织评分和mRNA水平。以60个月生存率分析患者预后。结果：所有病例的子宫内膜癌细胞中均以ephrinB2和EphB4为主定位。EphrinB2、EphB4组织评分分别与EphrinB2、EphB4 mRNA水平高度相关（r = 0.864、r = 0.615, P < 0.01）。随着临床分期（I < II < III, P < 0.01）、去分化(G(1) < G（2) < G(3), P < 0.01）和子宫内膜浸润（A < B < C, ephrinB2 < 0.01, EphB4 P < 0.05）， ephrinB2和EphB4的组织评分和mRNA水平均显著升高。34例ephrinB2和EphB4高表达患者的60个月生存率较差（分别为59%和62%），而34例ephrinB2和EphB4低表达患者的60个月生存率明显较高（分别为85%和82%）。结论：EphrinB2和EphB4在肿瘤进展过程中呈高表达，表现为去分化和肌层浸润。因此，ephrinB2/EphB4可能与肿瘤进展有关，并可能被认为是子宫内膜癌的一种新的预后指标。
Background: The ligand ephrinB2 and the corresponding receptor EphB4 contribute to tumor growth in various human tumors. This prompted us to study the expression and localization of ephrinB2 and EphB4 in uterine endometrial cancers to analyze the ephrinB2/EphB4 functions against clinical backgrounds.Materials and methods: We carried out immunohistochemistry and real-time RT-PCR to determine the histoscores and messenger RNA (mRNA) levels of ephrinB2 and EphB4, respectively, in 68 uterine endometrial cancers and 16 normal endometrium tissue samples. Patient prognoses were analyzed with a 60-month survival rate.Results: The localization of ephrinB2 and EphB4 was dominantly in the cancer cells of uterine endometrial cancer of all cases given. EphrinB2 and EphB4 histoscores were highly correlated with ephrinB2 and EphB4 mRNA levels, respectively (r = 0.864 and r = 0.615, P < 0.01). Both the histoscores and mRNA levels of ephrinB2 and EphB4 significantly increased with clinical stages (I < II < III, P < 0.01), dedifferentiation (G(1) < G(2) < G(3), P < 0.01) and myometrial invasion (A < B < C, P < 0.01 for ephrinB2 and P < 0.05 for EphB4) in uterine endometrial cancers. The 60-month survival rates of the 34 patients with high ephrinB2 and EphB4 expression were poor (59% and 62% respectively), while for the other 34 patients with low ephrinB2 and EphB4 expression, they were significantly higher (85% and 82%, respectively).Conclusions: EphrinB2 and EphB4 were overexpressed during the tumor advancement as dedifferentiation and myometrial invasion. Therefore, ephrinB2/EphB4 might work on tumor advancement and may be recognized as a novel prognostic indicator for uterine endometrial cancers.