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Prognostic impact of urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) in cytosols and pellet extracts derived from 892 breast cancer patients
Authors
C G J Sweep
EL Kaplan
+37 more
F Jänicke
F Jänicke
F Jänicke
F Jänicke
F Jänicke
F Jänicke
F Spyratos
H A Peters
H De Witte
HA Chapman
J A Foekens
J G M Klijn
J Grøndahl-Hansen
J H de Witte
J J T M Heuvel
JA Foekens
JA Foekens
JA Foekens
K Danø
K Danø
LA Liotta
M Fernö
M P Look
M Schmitt
MJ Duffy
MJ Duffy
MJ Duffy
MM Bradford
N Grebenschikov
N Grebenschikov
P Mignatti
PA Andreasen
PA Andreasen
Th H van Tienoven
Th J Benraad
ThJ Benraad
W L J van Putten
Publication date
1 January 1999
Publisher
Nature Publishing Group
Doi
Cite
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on
PubMed
Abstract
To evaluate the clinical relevance of urokinase-type plasminogen activator (uPA) and its type-1 inhibitor (PAI-1) measured by a recently developed enzyme-linked immunosorbent assay (ELISA), we analysed both components in samples derived from 892 patients with primary breast cancer (median follow-up 99 months). The assays were performed in cytosolic extracts as well as in corresponding detergent extracts of pellets obtained after ultracentrifugation, which was carried out when preparing the cytosolic fractions for routine steroid hormone receptor determination. Statistically significant correlations were found between the cytosolic levels and those determined in the pellet extracts (Spearman correlation coefficient rs = 0.60, P < 0.0001 for uPA and rs = 0.65, P < 0.0001 for PAI-1). Furthermore, strong correlations were found between the levels of both uPA (rs = 0.85, P < 0.0001) and PAI-1 (rs = 0.90, P < 0.0001) in the cytosols and their levels previously measured with ELISAs based on commercial reagents. In both Cox univariate and multivariate analysis, high cytosolic levels of uPA or PAI-1 were significantly associated with increased rates of relapse and death. The levels of uPA and PAI-1 in the pellet extracts also provided prognostic information, although to a lesser extent compared with the cytosolic extracts. The prediction of prognosis on the basis of uPA and PAI-1 assessed by an alternative ELISA once again emphasizes the established prognostic role and usefulness of these parameters in selection of breast cancer patients at high or low risk of recurrence. © 1999 Cancer Research Campaig
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