卵巢癌组织中尿激酶型纤溶酶原激活物、受体及其抑制物-1的表达以及与化疗耐药的关系

Immunohistochemical expression of urokinase plasminogen activator system uPA ,uPAR and PAI-1 in ovarian epithelial carcinoma: correlation with drug resistance of chemotherapy

目的:探讨卵巢上皮性癌(卵巢癌)组织中纤溶酶原激活系统——尿激酶型纤溶酶原激活物(uPA)、受体(uPAR)及其抑制物-1(PAI-1)的表达与卵巢癌化疗耐药的关系及其临床意义。方法:卵巢癌患者 77例,根据临床治疗和随访结果分为化疗耐药组(26例)与非耐药(51例)组,采用免疫组化法测定两组癌组织中uPA、PAI-1和uPAR的表达,并探讨其与化疗耐药的关系;采用多因素Logistic回归分析法探讨卵巢癌患者的年龄、手术病理分期、病理类型及分级、残留灶直径、化疗方案和三者表达与卵巢癌化疗耐药的关系;同时对预后进行多因素的COX生存分析。结果:uPA、PAI-1的阳性表达率,耐药组分别为96%(25/ 26)和92％(24/26),均明显高于非耐药组的80％(41/51)和82％(42/51,P值均<0．01);uPAR的阳性表达率, 耐药组为31％(8/26),非耐药组为35％(18/51),两组差异无显著性(P=0．668)。多因素分析显示uPA、PAI-1 表达与卵巢癌的手术病理分期均为与耐药(P值均<0．05)及预后(P值分别为0．045、0．031、0．001)相关的独立危险因素。结论:卵巢癌组织中uPA、PAI-1的高表达是卵巢癌化疗耐药及预后的危险因素。

Obdective： To investigate PAI-1 and uPAR in tumor tissues and the the possible correlation between the expression of uPA, response to chemotherapy and survival of patients with ovarian epithelial carcinoma. Methods：Seventy-seven patients were divided into drug resistant group （n=26） and drug sensitive group （n=51）. The antigens of uPA, PAI-1 and uPAR in ovarian tumour tissues were tested with immunohistochemistry. Logistic regression was employed to analyze the correlation between drug resistance and factors, including patients＇age, clinical stage,pathological degree and type of tumors, chemotherapy methods, operative results and the expression of uPA , PAI-1 and uPAR in tumors. The prognosis of disease was analyzed with multivariate COX regression. Results：In the drug resistance group, the expressions of uPA and PAI-1 were significantly higher than that in the drug sensitive group （P=0.004 and 0.001）. The expression of uPAR was not statistically different in the two groups （P=0.668）. Based on multivariate analysis, the expression of uPA and PAI-1 and clinical stage were three independent factors correlated with drug resistance and prognosis of disease for the patients with ovarian epithelial carcinoma（P=0.014, 0.030, 0.042 for drug resistance ;and P=0.045, 0.031, 0.001 for prognosis respectively）. Conclusion：The high expressions of uPA and PAI-1 in ovarian epithelial carcinoma are risk factors for drug resistance and poor prognosis of disease.