title: High tumor tissue concentration of urokinase plasminogen activator receptor is associated with good prognosis in patients with ovarian cancer.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Lund, Sweden. christer.borgfeldt@gyn.lu.se
authors.forename: Christer
authors.initials: C
authors.lastname: Borgfeldt
authors.forename: Pär-Ola
authors.initials: PO
authors.lastname: Bendahl
authors.forename: Barbro
authors.initials: B
authors.lastname: Gustavsson
authors.forename: Eva
authors.initials: E
authors.lastname: Långström
authors.forename: Mårten
authors.initials: M
authors.lastname: Fernö
authors.forename: Roger
authors.initials: R
authors.lastname: Willén
authors.forename: Seija
authors.initials: S
authors.lastname: Grenman
authors.forename: Bertil
authors.initials: B
authors.lastname: Casslén
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism / Q000556:secondary; D002288:Adenocarcinoma, Mucinous / Q000378:metabolism / Q000556:secondary; D018269:Carcinoma, Endometrioid / Q000378:metabolism / Q000556:secondary; D002454:Cell Differentiation; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism / Q000556:secondary; D018450:Disease Progression; D005260:Female; D006801:Humans; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D017396:Plasminogen Activator Inhibitor 2 / Q000378:metabolism; D011379:Prognosis; D018075:RNA, Complementary / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D015996:Survival Rate; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D018075:RNA, Complementary; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator