Borgfeldt Christer, Bendahl Pär-Ola, Gustavsson Barbro, Långström Eva, Fernö Mårten, Willén Roger, Grenman Seija, Casslén Bertil
Department of Obstetrics and Gynecology, University Hospital Lund, Sweden.
Int J Cancer. 2003 Nov 20;107(4):658-65. doi: 10.1002/ijc.11420.
The urokinase plasminogen activator (uPA) system is involved in tumor growth and metastasis. We assayed the components of the uPA system in homogenates of 64 primary epithelial ovarian tumors and 5 metastases and evaluated the association of these parameters to prognosis in the 51 malignant cases. The levels of uPA, PAI-2 and the uPA:PAI-1 complex increased with progressive loss of histological differentiation (p(trend) <0.001, <0.05 and <0.001). The level of PAI-1 was higher in poorly than in well/moderately differentiated tumors (p = 0.03). The content of uPAR was lower in benign tumors as compared to borderline malignancies (p = 0.002), invasive primary tumors (p < 0.001), and metastases (p = 0.002). Surprisingly, the level of uPAR was lower in poorly differentiated as compared to both borderline (p = 0.01) and well differentiated malignant tumors (p = 0.005). Also, the level of uPAR was lower in advanced as compared to early stages of the disease (p(trend) = 0.002). The median follow-up time for patients was 5.8 years. High tumor tissue levels of uPAR were associated with longer postoperative survival (HR = 0.4, 95% CI = 0.2-0.8, p = 0.01). In contrast, shorter survival was evident in patients with high tumor levels of uPA from 2 years on after operation (HR = 4.6, 95% CI = 1.2-17, p = 0.02). High tPA levels tended to be associated with shorter overall survival after 2 years (HR = 2.9, 95% 95% CI = 0.9-9.8, p = 0.08). Although high tumor tissue content of uPAR was associated with a less aggressive phenotype characterized by well differentiated histology and longer survival, low content of uPAR in the poorly differentiated tumors and metastases presumably results from increased elimination of uPAR.
尿激酶型纤溶酶原激活剂（uPA）系统与肿瘤生长和转移有关。我们检测了64例原发性上皮性卵巢肿瘤和5例转移瘤匀浆中uPA系统的成分，并评估了这些参数与51例恶性病例预后的相关性。uPA、PAI-2和uPA:PAI-1复合物的水平随着组织学分化程度的逐渐降低而升高（趋势p<0.001、<0.05和<0.001）。PAI-1的水平在低分化肿瘤中高于高分化/中分化肿瘤（p = 0.03）。与交界性恶性肿瘤（p = 0.002）、侵袭性原发性肿瘤（p < 0.001）和转移瘤（p = 0.002）相比，良性肿瘤中uPAR的含量较低。令人惊讶的是，与交界性（p = 0.01）和高分化恶性肿瘤（p = 0.005）相比，低分化肿瘤中uPAR的水平较低。此外，与疾病早期相比，晚期疾病中uPAR的水平较低（趋势p = 0.002）。患者的中位随访时间为5.8年。肿瘤组织中uPAR水平高与术后生存期延长相关（风险比[HR]=0.4，95%置信区间[CI]=0.2 - 0.8，p = 0.01）。相反，术后2年起，肿瘤uPA水平高的患者生存期明显较短（HR = 4.6，95% CI = 1.2 - 17，p = 0.02）。2年后，高组织型纤溶酶原激活剂（tPA）水平往往与总生存期较短相关（HR = 2.9，95% CI = 0.9 - 9.8，p = 0.08）。虽然肿瘤组织中uPAR含量高与以高分化组织学和较长生存期为特征的侵袭性较低的表型相关，但低分化肿瘤和转移瘤中uPAR含量低可能是由于uPAR清除增加所致。
