Berclaz G, Karamitopoulou E, Mazzucchelli L, Rohrbach V, Dreher E, Ziemiecki A, Andres A-C
Department of Obstetrics and Gynecology, University Hospital, Berne, Switzerland.
Ann Oncol. 2003 Feb;14(2):220-6. doi: 10.1093/annonc/mdg072.
Members of the Eph family of tyrosine kinases have been implicated in embryonic pattern formation and vascular development; however, little is known about their role in the adult organism. We have observed estrogen-dependent EphB4 expression in the normal breast suggesting its implication in the hormone-controlled homeostasis of this organ. Since the endometrium is a similarly hormone dependent organ and endometrial carcinoma is thought to result from estrogenic stimulation, we have investigated EphB4 expression in normal human endometrium and during its carcinogenesis.
EphB4 expression was analyzed immunohistochemically in 26 normal endometrium specimens, 15 hyperplasias and 102 endometrioid adenocarcinomas and correlated with clinical and prognostic tumor characteristics.
In normal endometrial tissue no EphB4 protein was detected. Strikingly, we observed a drastic increase (P <0.0001) in the number of EphB4 protein-expressing glandular epithelial cells in the majority of hyperplasias and carcinomas. Moreover, we found a statistically highly significant positive correlation between EphB4 expression and post-menopausal stage of the patient (P = 0.007).
These findings indicate that in the endometrium, EphB4 is an early indicator of malignant development and, thus, EphB4 may represent a potent tool for diagnosis and therapeutic intervention.
酪氨酸激酶Eph家族成员已被证实参与胚胎模式形成和血管发育；然而，它们在成体中的作用却鲜为人知。我们观察到在正常乳腺中存在雌激素依赖性的EphB4表达，提示其参与该器官的激素调控稳态。由于子宫内膜是一个同样依赖激素的器官，且子宫内膜癌被认为是由雌激素刺激所致，我们研究了EphB4在正常人类子宫内膜及其癌变过程中的表达。
采用免疫组织化学方法分析了26例正常子宫内膜标本、15例增生组织和102例子宫内膜样腺癌中EphB4的表达，并将其与临床和肿瘤预后特征进行关联分析。
在正常子宫内膜组织中未检测到EphB4蛋白。令人惊讶的是，我们观察到在大多数增生组织和癌组织中，表达EphB4蛋白的腺上皮细胞数量急剧增加（P <0.0001）。此外，我们发现EphB4表达与患者绝经后阶段之间存在统计学上高度显著的正相关（P = 0.007）。
这些发现表明，在子宫内膜中，EphB4是恶性发展的早期指标，因此，EphB4可能是一种有效的诊断和治疗干预工具。
