Shiba E, Kim S J, Taguchi T, Izukura M, Kobayashi T, Furukawa J, Yayoi E, Shin E, Takatsuka Y, Koyama H, Takai S
Department of Surgical Oncology, Osaka University Medical School, Japan.
J Cancer Res Clin Oncol. 1997;123(10):555-9. doi: 10.1007/s004320050104.
Urokinase-type plasminogen activator (u-PA), which cleaves plasminogen to yield plasmin, is a serine protease of fibrinolysis and is presumed to play a key role in extracellular proteolysis and facilitate the migration of cancer cells. This study was conducted prospectively to evaluate the prognostic significance of u-PA antigen level in breast cancer tissues. u-PA concentrations in the cytosol of 226 breast cancer tissues were determined prospectively by enzyme-linked immunosorbent assay using cytosol fractions prepared for steroid hormone assay. The median follow-up period of the patients was 60 months. Various prognostic factors were evaluated by univariate analysis or multivariate analysis using the Cox proportional-hazards method. Patients with primary breast cancer containing high levels of u-PA had a significantly shorter disease-free survival than patients with low levels of u-PA antigens. In multivariate analysis, a high level of u-PA was an independent risk factor for disease-free survival, being independent of age, axillary node status, and estrogen receptor status. Among the major prognostic factors, a high u-PA antigen level, lymph node involvement, and a positive estrogen receptor status were the most important for predicting relapse-free survival (P = 0.044, P < 0.0001, P = 0.0039). This first prospective study confirmed the prognostic significance of the u-PA antigen level in association with other major prognostic factors. The results of our present study suggest that u-PA in breast cancer tissue might be involved in breast cancer invasion and metastasis.
尿激酶型纤溶酶原激活物（u-PA）可裂解纤溶酶原生成纤溶酶，它是一种纤维蛋白溶解的丝氨酸蛋白酶，被认为在细胞外蛋白水解中起关键作用，并促进癌细胞迁移。本研究前瞻性地评估了乳腺癌组织中u-PA抗原水平的预后意义。通过酶联免疫吸附测定法，使用为类固醇激素测定制备的细胞溶质级分，前瞻性地测定了226例乳腺癌组织细胞溶质中的u-PA浓度。患者的中位随访期为60个月。使用Cox比例风险法通过单变量分析或多变量分析评估各种预后因素。原发性乳腺癌中u-PA水平高的患者无病生存期明显短于u-PA抗原水平低的患者。在多变量分析中，高水平的u-PA是无病生存的独立危险因素，独立于年龄、腋窝淋巴结状态和雌激素受体状态。在主要预后因素中，高u-PA抗原水平、淋巴结受累和雌激素受体阳性状态对预测无复发生存最为重要（P = 0.044，P < 0.0001，P = 0.0039）。这项首次前瞻性研究证实了u-PA抗原水平与其他主要预后因素相关的预后意义。我们目前的研究结果表明，乳腺癌组织中的u-PA可能参与乳腺癌的侵袭和转移。
