EphA2受体表达与卵巢癌侵袭性的关系

Expression and Significance of EphA2 Receptor in Ovarian Carcinoma

目的探讨酪氨酸蛋白激酶受体EphA2在卵巢癌组织中的表达意义及其与卵巢癌微血管生成之间的相关性。方法应用免疫组化方法检测76例卵巢癌标本和20例卵巢良性病变中EphA2蛋白的表达情况,并分析EphA2表达与卵巢癌临床病理学因素及微血管生成之间的关系。结果卵巢癌中EphA2的阳性表达率77.6%(59/76)明显高于卵巢良性病变的表达率25.0%(5/20),P<0.01。晚期卵巢癌(III/IV期)EphA2的阳性表达率84.4%(54/64)明显高于早中期卵巢癌(I/II期)41.7%(5/12),P<0.01。高级别卵巢癌(III级)E-phA2的阳性表达率82.5%(52/63)高于低级别卵巢癌(I/II级)的阳性表达率53.8%(7/13),P<0.05。EphA2表达与患者的年龄、肿瘤的组织学类型、淋巴结转移及有无腹水无明显相关性(P>0.05)。免疫组化结果还发现,除卵巢癌细胞外,肿瘤组织内微血管内皮细胞也有EphA2受体蛋白表达。CD34染色后卵巢癌的微血管密度(MVD)与EphA2表达水平有显著相关性(P<0.05),EphA2阳性表达强度高的肿瘤区域有较高的微血管密度。结论EphA2过表达提示卵巢癌具有较强的侵袭性,或可作为卵巢癌一个重要的治疗靶点。

Objective To investigate the expression and significance of erythropoietin - pro- ducing hepatocellular A2 （EphA2） receptor tyrosine kinase in human ovarian carcinoma and the correlation between EphA2 expression and tumor angiogenesis. Methods Immunohistochemistry was used to examine the EphA2 expression in 76 surgically resected human ovarian carcinoma tissues and 20 benigh disease tissues. Microvessels in the ovarian carcinoma tissues were counted after immunostaining for CD34, and the correlation between EphA2 expression and Microvessel counts（MVCs） in ovarian carcinoma tissues were assessed. Results Our immunohistochemical analyses demonstrated the positive rate of EphA2 expression was significantly higher in ovarian carcinomas（77.6% ,59/76） than that in benigh diseases （25.0%, 5/20 ）. We also found that EphA2 related to high tumor - stage and grade, 84.4% （54/64） of the high -stage （Ⅲ or Ⅳ） ovarian cancers overexpressed EphA2 compared with 41.7% （5/12） of the low - stage cancers （ P 〈 0.01 ）. Similarly, 82.5% （52/63） of the high - grade（ Ⅲ ） tumors overexpressed EphA2 compared with 53.8% （ 7/13 ） of the low - grade cancers （ P 〈 0.05 ）. There was no association of EphA2 expression with patient age, histological subtype, node metastasis and presence of ascites （ P 〉 0.05）. We observed specific EphA2 staining was present in both ovarian cancer cells and tumor vascular endothelial cells. Microvessel density （MVD） after immunostaining for CD34 were significantly correlated with overexpression of EphA2 （ P 〈 0.05 ）, high microvessel density were present in EphA2 - strong positive tumor areas. Conclusion EphA2 overexpression is predictive of aggressive ovarian cancer behavior and may be an important therapeutic target.