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.
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Authors | Christer Borgfeldt, Pär-Ola Bendahl, Barbro Gustavsson, Eva Långström, Mårten Fernö, Roger Willén, Seija Grenman, Bertil Casslén |
Journal | International journal of cancer
(Int J Cancer)
Vol. 107
Issue 4
Pg. 658-65
(Nov 20 2003)
ISSN: 0020-7136 [Print] United States |
PMID | 14520707
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 2003 Wiley-Liss, Inc. |
Chemical References |
- PLAUR protein, human
- Plasminogen Activator Inhibitor 1
- Plasminogen Activator Inhibitor 2
- RNA, Complementary
- RNA, Messenger
- Receptors, Cell Surface
- Receptors, Urokinase Plasminogen Activator
- Tissue Plasminogen Activator
- Urokinase-Type Plasminogen Activator
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Topics |
- Adenocarcinoma, Clear Cell
(metabolism, secondary)
- Adenocarcinoma, Mucinous
(metabolism, secondary)
- Carcinoma, Endometrioid
(metabolism, secondary)
- Cell Differentiation
- Cystadenocarcinoma, Serous
(metabolism, secondary)
- Disease Progression
- Female
- Humans
- Neoplasm Invasiveness
- Neoplasm Staging
- Neoplasms, Glandular and Epithelial
(metabolism, pathology, secondary)
- Ovarian Neoplasms
(metabolism, pathology, secondary)
- Phenotype
- Plasminogen Activator Inhibitor 1
(metabolism)
- Plasminogen Activator Inhibitor 2
(metabolism)
- Prognosis
- RNA, Complementary
(metabolism)
- RNA, Messenger
(metabolism)
- Receptors, Cell Surface
(metabolism)
- Receptors, Urokinase Plasminogen Activator
- Survival Rate
- Tissue Plasminogen Activator
(metabolism)
- Urokinase-Type Plasminogen Activator
(metabolism)
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