High tumor tissue concentration of urokinase plasminogen activator receptor is associated with good prognosis in patients with ovarian cancer.
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.
Borgfeldt
Christer
C
Department of Obstetrics and Gynecology, University Hospital Lund, Sweden. christer.borgfeldt@gyn.lu.se
Bendahl
Pär-Ola
PO
Gustavsson
Barbro
B
Långström
Eva
E
Fernö
Mårten
M
Willén
Roger
R
Grenman
Seija
S
Casslén
Bertil
B
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
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