Significance of EphA2 receptor expression in human gliomas / 肿瘤

ABSTRACT

Objective: To investigate the expression and significance of erythropoietin-producing hepatocellular A2 (EphA2), a receptor of tyrosine kinase in human gliomas and the correlation between EphA2 expression and tumor angiogenesis. Methods: Immunohistochemistry was used to examine the EphA2 expression in 66 surgically resected human glioma tissues, 2 human glioblastoma multiforme (GBM) cell lines(U251 and U87) and 10 normal brain tissues. Next, we performed Western blotting to further investigate the expression of EphA2 in high-grade GBM and normal brain tissues. Microvessels in the glioma tissues were counted after immunostaining for CD34, and the c orrelation between EphA2 expression and microvessel counts (MVCs) in glioma tissues were assessed. Results: Our immunohistochemical analyses demonstrated variable levels of EphA2 expression in 63 of 66 cases examined (63/66, 95.5%). But EphA2 expression was not detected in all 10 normal brain samples and 3 cases of low-grade gliomas (I-II). There was statistical difference in EphA2 expression between human gliomas and normal brain samples (P < 0.01). The positive rate of EphA2 expression was significantly higher in high-grade gliomas (WHO III-IV) than in low-grade gliomas (WHO I-II) (P < 0.01). The specific EphA2 staining was observed in both glioma tissues and U251 cells. The expression level of EphA2 protein was significantly lower in U87 cells than that in U251 cells. It was not detected in normal brain tissues. Microvessel density (MVD) significantly correlated with expression level of EphA2 protein (P <0.01). The MVD was higher in EphA2-strong positive tumor areas. Conclusion: EphA2 is specifically over-expressed in high-grade gliomas, but is not detected in normal brain tissues. EphA2 may be a novel marker of malignant glioma. It can be used as a molecular target for therapeutic intervention against high-grade glioma. EphA2 is involved in angiogenesis and plays an important role in the initiation and progression of glioma.