Department of Gynecologic Oncology, Anderson Cancer Center, Houston, TX, USA.
Cancer Biol Ther. 2010 Dec 15;10(12):1306-14. doi: 10.4161/cbt.10.12.13582.
EphA2 overexpression predicts poor prognosis in endometrial cancer. To explore mechanisms for this association and assess its potential as therapeutic target, the relationship of EphA2 expression to markers of angiogenesis was examined using patient samples and an orthotopic mouse model of uterine cancer.
Expression of EphA2, estrogen receptor (ER), progesterone receptor (PR), Ki-67, vascular endothelial growth factor (VEGF) and microvessel density (MVD) was evaluated using immunohistochemistry in 85 endometrioid endometrial adenocarcinomas (EEC) by two independent investigators. Results were correlated with clinicopathological characteristics. The effect of EphA2- agonist monoclonal antibody EA5, alone or in combination with docetaxel was studied in vitro and in vivo. Samples were analyzed for markers of angiogenesis, proliferation and apoptosis.
Of 85 EEC samples, EphA2 was overexpressed in 47% of tumors and was significantly associated with high VEGF expression (p=0.001) and high MVD counts (p=0.02). High EphA2 expression, high VEGF expression and high MVD counts were significantly associated with shorter disease-specific survival. EA5 led to decrease in EphA2 expression and phosphorylation in vitro. In the murine model, while EA5 (33-88%) and docetaxel (23-55%) individually led to tumor inhibition over controls, combination therapy had the greatest efficacy (78-92%, p.
EphA2 过表达预示着子宫内膜癌预后不良。为了探讨这种关联的机制，并评估其作为治疗靶点的潜力，本研究使用患者样本和子宫癌的原位小鼠模型，检查了 EphA2 表达与血管生成标志物的关系。
通过两位独立研究者，使用免疫组化法对 85 例子宫内膜样子宫内膜腺癌（EEC）中 EphA2、雌激素受体（ER）、孕激素受体（PR）、Ki-67、血管内皮生长因子（VEGF）和微血管密度（MVD）的表达进行评估，并将结果与临床病理特征相关联。研究了 EphA2-激动型单克隆抗体 EA5 单独或与多西紫杉醇联合应用的效果，在体外和体内进行了研究。对血管生成、增殖和凋亡标志物进行了分析。
在 85 例 EEC 样本中，47%的肿瘤存在 EphA2 过表达，并且 EphA2 过表达与高 VEGF 表达（p=0.001）和高 MVD 计数（p=0.02）显著相关。高 EphA2 表达、高 VEGF 表达和高 MVD 计数与较短的疾病特异性生存时间显著相关。EA5 在体外导致 EphA2 表达和磷酸化减少。在小鼠模型中，虽然 EA5（33-88%）和多西紫杉醇（23-55%）单独治疗相对于对照组均能抑制肿瘤，但联合治疗的疗效最大（78-92%，p
