上皮性卵巢癌组织中uPA和PAI-1的表达及意义

Expression and Clinical Significance of uPA and PAI-1 in Epithelial Ovarian Cancer

背景与目的:近年研究表明,尿激酶型纤溶酶原激活物(urokinase-typeplasminogen activator,uPA)及其抑制物(plasminogen activator inhibitor,PAI)在肿瘤侵袭、转移过程中起重要作用,但其与上皮性卵巢癌的关系研究甚少。本研究从蛋白水平探讨uPA、PAI-1在上皮性卵巢癌浸润、转移中的作用,组织中的分布情况、及与预后的关系。方法:应用免疫组化法检测80例上皮性卵巢癌、20例良性卵巢肿瘤组织uPA、PAI-1蛋白表达,并结合临床病理因素、预后进行分析。结果:上皮性卵巢癌、良性卵巢肿瘤组织中uPA阳性率分别为77.5%和30.0%(P<0.001),PAI-1阳性率分别为55.0%和20.0%(P=0.005)。上皮性卵巢癌组织中uPA表达与PAI-1表达呈显著性正相关(P=0.001)。uPA阳性与盆腹腔转移病灶直径>1cm有关(P=0.038),与患者年龄、FIGO分期、组织学类型、病理分级、术前血CA125值、卵巢病灶大小、残留病灶大小无显著性相关(P>0.05);PAI-1阳性与FIGO分期有显著性相关(P=0.022),与上述其他临床病理因素无显著性相关(P>0.05)。多因素Cox回归模型显示,uPA表达是肿瘤无进展生存、总生存的独立危险因素;PAI-1表达是总生存的独立危险因素。结论:上皮性卵巢癌组织中uPA、PAI-1表达上调。uPA、PAI-1有可能作为预测上皮性卵巢癌预后的参考指标。

BACKGROUND ＆ OBJECTIVE： Recent.researches showed that urokinase-type plasminogen activator （uPA） and its inhibitor, plasminogen activator inhibitor （PAI）-1, play an important role in the invasion and metastasis of solid tumors. However, their correlations to epithelial ovarian cancer have seldom been reported. This study was to investigate the roles of uPA and PAI-1 in the invasion and metastasis of epithelial ovarian cancer, to clarify their localization and relationship with prognosis. METHODS. Immunohistochemistry was applied to examine the protein expression of uPA and PAI-1 in 80 specimens of epithelial ovarian cancer and 20 specimens of benign ovarian tumor. The correlations of their expression to the clinicopathologic characteristics and prognosis of the patients were analyzed. RESULTS. The positive rates of uPA and PAI-1 were significantly higher in epithelial ovarian cancer than in benign ovarian tumor （77.5% vs. 30.0%, P〈 0.001 ; 55.0% vs. 20.0%, P=0.005）. uPA expression was correlated positively to PAI-1 expression in epithelial ovarian cancer （P=0.001）. Higher positive rate of uPA was associated with greater metastatic tumor in the peritoneal cavity （P=0.038）, but not associated with age, FIGO stage, histological type, pathologic grade, serum CA125 level, ovarian tumor size, and the size of residual tumor （P〉0.05）. Higher positive rate of PAI-1 was associated with early FIGO stage （P=0.022）, but not associated with other parameters （P〉 0.05）. Multivariate analysis showed that uPA was an independent factor for progression-free survival and overall survival, and PAI-1 was an independent factor for overall survival. CONCLUSION. Both uPA and PAI-1 are upregulated in epithelial ovarian cancer, and might be used as markers to predict the prognosis of epithelial ovarian cancer patients.