title: The complex between urokinase and its type-1 inhibitor in primary breast cancer: relation to survival.
abstract: We examined the relationship between tumor tissue level of the complex formed of urokinase (uPA) and its type-1 inhibitor (PAI-1) and survival of breast cancer patients. The study included 342 axillary lymph node-negative and -positive primary breast cancer patients with a median follow-up of 67 months. Using a newly established ELISA, the levels of preformed uPA-PAI-1 complex were measured in tumor tissue extracts and analyzed with respect to total uPA, total PAI-1, and clinicopathological parameters, including survival. uPA-PAI-1 complex comprised a minor, variable fraction of both total uPA and PAI-1 levels. The complex levels were higher in node-negative tumors than in node-positive tumors and higher in small and low-grade tumors (all, P < or = 0.002). The tumor levels of complex, uPA, and PAI-1 were all associated with survival; high complex levels predicted longer recurrence-free survival (P = 0.03) and overall survival [OS (P = 0.005)], whereas high uPA or PAI-1 levels significantly predicted shorter survival. In multivariate Cox analysis, the only parameters that independently predicted survival were total PAI-1 level and lymph node status for recurrence-free survival and OS and, additionally, steroid hormone receptor status and grade for OS. This is the first demonstration of a relationship between uPA.PAI-1 complex tumor level and patient survival. However, total PAI-1 level showed superior prognostic power. Additional studies are needed to understand the relationship of these parameters to cancer biology and to assess the clinical utility of the uPA PAI-1 complex.
authors.affiliation: The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.
authors.forename: A N
authors.initials: AN
authors.lastname: Pedersen
authors.forename: I J
authors.initials: IJ
authors.lastname: Christensen
authors.forename: R W
authors.initials: RW
authors.lastname: Stephens
authors.forename: P
authors.initials: P
authors.lastname: Briand
authors.forename: H T
authors.initials: HT
authors.lastname: Mouridsen
authors.forename: K
authors.initials: K
authors.lastname: Danø
authors.forename: N
authors.initials: N
authors.lastname: Brünner
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality*; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000378:metabolism*; D011485:Protein Binding; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D014568:Urokinase-Type Plasminogen Activator