卵巢恶性肿瘤组织中uPA PAI-1蛋白表达与其临床病理因素的关系

The Expression of uPA and PAI-1 Protein in Ovarian Cancer and Its Relationship with Clinicopathological Features

目的:最近研究表明尿激酶型纤溶酶原激活因子(urokinase-type plasminogen activator,uPA)及其1型抑制因子(PAI-1)在恶性肿瘤的发生、发展及转移过程中起重要作用,且其过度表达与预后差有关。本研究从蛋白水平探讨uPA及PAI-1表达与卵巢肿瘤发生、发展及预后的关系。方法:采用SABC免疫组织化学方法检测40例卵巢恶性肿瘤(Ⅰ～Ⅱ期14例,III～IV期26例)、20例良性肿瘤及20例正常卵巢组织uPA及PAI-1蛋白的表达。结果:1)uPA、PAI-1在恶性肿瘤中的表达率为52.5%及67.5%,明显高于良性肿瘤及正常组织,差异均有显著性(P<0.05),而良性肿瘤与正常组织无明显差异(P>0.05)。2)uPA、PAI-1在恶性卵巢肿瘤中表达与病理类型、腹水多少、有无淋巴结转移无关。3)uPA、PAI-1在III～IV期的表达率明显高于Ⅰ～Ⅱ期,大网膜及肝有转移者明显高于无转移者;uPA表达与肿瘤分化程度呈负相关,PAI-1与残存灶大小呈正相关。4)uPA阴性表达者的平均总生存期(49.0个月)明显高于阳性者(29.3个月);PAI-1阴性表达者的平均总生存期(52.2个月)明显高于阳性者(31.8个月),(P均<0.01)。5)COX模型分析显示PAI-1蛋白表达可作为独立的预后指标。结论:uPA、PAI-1与卵巢肿瘤的发生、恶化有关,可作为估计肿瘤转移潜能及预后的重要指标。

Objective： To investigate the role of urokinase-type plasminogen activator（uPA） and PAI-1 in the invasion and metastasis of epithelial ovarian cancer and its relationship with prognosis, Methods： SABC immunohistochemistry was employed to detect uPA and PAI-1 protein expression in 40 samples of ovarian cancer tissue, 20 samples of benign breast tumor and 20 samples of normal breast tissue. Results： The expression rate of uPA and PAI-1 protein in ovarian cancer was 52.5% and 67.5%, respectively, significantly higher than in the benign tumors and normal tissues（P〈0.05）. No significant difference was found in uPA and PAI-1 expression between the benign tumors and the normal tissues（P〉0.05）. In the ovarian cancer group, no correlation was observed between the expression of uPA and PAI-1 protein and pathological type, ascitic volume, or lymph node metastasis. The expression rate of uPA and PAI-1 protein in stage Ⅲ～Ⅳ patients was much higher than that in stage Ⅰ～Ⅱ patients, Compared to patients without omentum involvement or liver metastasis, patients with omentum involvement or liver metastasis presented with higher expression of uPA and PAI-1 proteins. The expression of uPA was negatively correlated with pathological grade, and the expression of PAI-1 was positively correlated with residual tumor volume, The median overall survival of patients with no detectable uPA expression （49.0 months） was longer that of those with uPA expression （29.3 months）, with a significant difference between the two groups（P〈0.01）. The median overall survival of patients with no detectable PAI-1 expression （52.2 months） was also longer than that of those with PAI-1 expression（39.8 months）, with a significant difference（P〈0.01）. The Cox regression model for multivariate anal- ysis showed that the expression of PAI-1 protein was an independent prognostic factor for ovarian cancer. Conclusion：uPA and PAI-I are involved in the carcinogenesis and progression of ovarian cancer, and they can be used as biomarkers for prognosis.