Association of urokinase-type plasminogen activator and its inhibitor with disease progression and prognosis in ovarian cancer.

Abstract

PURPOSE:

Urokinase-type plasminogen activator (uPA) and its inhibitor, plasminogen activator inhibitor (PAI)-1, have been shown to be related to poor prognosis in a variety of malignant solid tumors. Studies on the prognostic relevance of uPA and PAI-1 in ovarian cancer, however, have been inconclusive. The current study tests the hypothesis that elevated expression of uPA and PAI-1 is associated with prognosis and disease progression.

EXPERIMENTAL DESIGN:

uPA and PAI-1 were prospectively measured by quantitative ELISA in tumor samples from 103 ovarian cancer patients (82 primary invasive epithelial carcinomas, 9 low malignant potential tumors, and 12 recurrent ovarian carcinomas).

RESULTS:

uPA but not PAI-1 levels were consistently associated with malignant progression, with levels increased from low malignant potential tumors to primary tumors (uPA, P = 0.04; PAI-1, P = 0.019), from early to advanced disease stages (uPA, P = 0.014; PAI-1, P = 0.23), and from primary to intra-abdominal metastatic tumors (uPA, P = 0.001; PAI-1, P = 0.16). High uPA and PAI-1 levels were associated with residual tumor volumes of >1 cm (P = 0.001 and P = 0.016, respectively). Among invasive International Federation of Gynecologists and Obstetrician stages I-IV tumors, elevated levels of uPA (>5.5 ng/mg) and PAI-I (>18.8 ng/ml) were associated with a shortened progression-free survival (uPA, P = 0.003; PAI-1, P = 0.039) and overall survival (uPA, P = 0.0002; PAI-1, P = 0.007). In multivariate analysis, uPA retained prognostic independence for progression-free survival (P = 0.037) and overall survival (P = 0.006).

CONCLUSIONS:

These data suggest that the uPA/PAI-1 axis may play an important role in the intra-abdominal spread and reimplantation of ovarian cancer cells. The prognostic relevance of uPA and PAI-1 supports their possible role in the malignant progression of ovarian cancer.

• Authors: G Konecny, M Untch, A Pihan, R Kimmig, M Gropp, P Stieber, H Hepp, D Slamon, M Pegram
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 7 Issue 6 Pg. 1743-9 (Jun 2001) ISSN: 1078-0432 [Print] United States
• PMID: 11410515 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Plasminogen Activator Inhibitor 1
• Urokinase-Type Plasminogen Activator

Topics

• Adult
• Aged
• Aged, 80 and over
• Disease Progression
• Disease-Free Survival
• Enzyme Activation
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Middle Aged
• Multivariate Analysis
• Ovarian Neoplasms (diagnosis, metabolism, pathology)
• Plasminogen Activator Inhibitor 1 (biosynthesis)
• Prognosis
• Recurrence
• Time Factors
• Urokinase-Type Plasminogen Activator (antagonists & inhibitors, biosynthesis)