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

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。

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

Objective: To investigate the role of urokinase-type plasminogen activator(uPA) and PAI-1 in the inva-sion and metastasis of epithelial ovarian cancer and its relationship with prognosis. Methods: SABC immunohistochemistrywas employed to detect uPA and PAI-1 protein expression in 40 samples of ovarian cancer tissue, 20 samples of benignbreast tumor and 20 samples of normal breast tissue. Results: The expression rate of uPA and PAI-1 protein in ovariancancer was 52.5% and 67.5%, respectively, significantly higher than in the benign tumors and normal tissues(P<0.05). Nosignificant 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 pathologi-cal type, ascitic volume, or lymph node metastasis. The expression rate of uPA and PAI-1 protein in stage III~IV patientswas 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. Theexpression of uPA was negatively correlated with pathological grade, and the expression of PAI-1 was positively correlatedwith residual tumor volume. The median overall survival of patients with no detectable uPA expression (49.0 months) waslonger that of those with uPA expression (29.3 months), with a significant difference between the two groups(P<0.01). Themedian overall survival of patients with no detectable PAI-1 expression (52.2 months) was also longer than that of thosewith 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-1 are involved in the carcinogenesis and progression of ovarian cancer, and they can be used as biomarkersfor prognosis.