Hofmann R, Lehmer A, Buresch M, Hartung R, Ulm K
Department of Urology, Technische Universität München, Munich, Germany.
Cancer. 1996 Aug 1;78(3):487-92. doi: 10.1002/(SICI)1097-0142(19960801)78:3<487::AID-CNCR16>3.0.CO;2-V.
Urokinase plasminogen activator (u-PA) plays a key role in the metastatic process by promoting plasmin mediated tissue degradation. Metastatic cell invasion requires localized proteolysis, which may be directed by u-PA receptor. The binding of u-PA and PAI-1 to the u-PA-receptor may cause internalization of the trimeric complex into the cell and activate a tyrosine-kinase. In a prospective study the u-PA, u-PA-R, and PAI-1 content in patients with renal cell carcinoma (RCC) and benign renal tissue were correlated with traditional prognostic factors such as the TNM staging, histologic grading, ploidy, and the clinical outcome of the patients.
One hundred fifty-two patients who underwent transperitoneal tumor nephrectomy for RCC were followed up for a mean of 23.9 months. u-PA, u-PA-R, and PAI-1 from the tumor tissue and corresponding benign renal tissue were quantified from detergent extracted tissue samples (1% Trinton-X-100 in triethanolamine-buffered saline) and measured with an enzyme-linked immunoadsorbent assay.
PAI-1 significantly correlated with the prevalence of distant metastasis (M0: 10.04 vs. M1 23.79, P=0.02) and the development of new metastasis postoperatively (M0: 10.85 vs. M1 27.36, P=0.001). A cut-off level of 12 ng/mg protein for PAI-1 selected a group of patients at high risk for relapse. Forty-one patients had PAI-1 > 12 ng/mg with 6 relapses compared with 55 patients with PAI-1 < 12 ng/mg with 1 relapse during the follow-up. Content of mu-PA correlated with the development of distant metastases (log rank 4.32, P=0.037). A cut-off value of 0.84 ng/mg selected 2 groups: a group at high risk for metastasizing (u-PA > 0.84, n=11 with 9 events and a group at low risk (u-PA < 0.84 with 94 patients and 5 events). Applying a cut-off value of 0.85 for u-PA-R 2 groups could be discriminated: 31 patients had no relapse with u-PA-R < 0.85 and 18 had 3 recurrences with u-PA-R > 0.85 g/ml.
u-PA, u-PA-R, and PAI-1 are strong and independent prognostic factors for predicting early relapse for RCC. Especially with PAI-1, a high and low risk group for disease free survival can be discriminated.
尿激酶型纤溶酶原激活剂（u-PA）通过促进纤溶酶介导的组织降解在转移过程中起关键作用。转移性细胞侵袭需要局部蛋白水解，这可能由u-PA受体引导。u-PA和PAI-1与u-PA受体的结合可能导致三聚体复合物内化进入细胞并激活酪氨酸激酶。在一项前瞻性研究中，肾细胞癌（RCC）患者和良性肾组织中u-PA、u-PA-R和PAI-1的含量与传统预后因素如TNM分期、组织学分级、倍体以及患者的临床结局相关。
152例行经腹肿瘤肾切除术的RCC患者接受了平均23.9个月的随访。从去污剂提取的组织样本（三乙醇胺缓冲盐水中1%的曲拉通-X-100）中定量肿瘤组织和相应良性肾组织中的u-PA、u-PA-R和PAI-1，并采用酶联免疫吸附测定法进行测量。
PAI-1与远处转移的发生率显著相关（M0：10.04 vs. M1 23.79，P = 0.02）以及术后新转移的发生相关（M0：10.85 vs. M1 27.36，P = 0.001）。PAI-1的蛋白水平截断值为12 ng/mg时，选择出一组复发风险高的患者。41例患者PAI-1 > 12 ng/mg，随访期间有6例复发，而55例患者PAI-1 < 12 ng/mg，仅有1例复发。u-PA的含量与远处转移的发生相关（对数秩检验4.32，P = 0.037）。截断值为0.84 ng/mg时可分为两组：一组转移风险高（u-PA > 0.84，n = 11，有9例转移事件）和一组低风险组（u-PA < 0.84，94例患者，有5例转移事件）。应用u-PA-R的截断值0.85可区分两组：31例u-PA-R < 0.85的患者无复发，18例u-PA-R > 0.85 g/ml的患者有3次复发。
u-PA、u-PA-R和PAI-1是预测RCC早期复发的强有力且独立的预后因素。尤其是PAI-1，可区分疾病无进展生存的高风险和低风险组。
