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Urokinase and Plasminogen Activator Inhibitor Type 1 in Pulmonary Adenocarcinoma

Helle Pedersen, Jan Grøndahl-Hansen, Dorte Francis, Kell Østerlind, Heine Høi Hansen, Keld Danø and Nils Brünner
Helle Pedersen
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Jan Grøndahl-Hansen
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Dorte Francis
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Kell Østerlind
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Heine Høi Hansen
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Keld Danø
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Nils Brünner
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DOI:  Published January 1994
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Abstract

The urokinase pathway of plasminogen activation is involved in proteolytic degradation of various tissues, including dissolution of the extracellular matrix and basement membranes during the process of cancer cell invasion. We have studied the prognostic value of urokinase-type plasminogen activator (uPA) and type-1 plasminogen activator inhibitor (PAI-1) in tumor extracts from 106 patients with adenocarcinoma of the lung. uPA and PAI-1 levels were determined by sandwich enzyme-linked immunosorbent assays. No correlation was found between uPA and PAI-1 (r = 0.23). High PAI-1 levels were significantly associated with short-duration overall survival (P = 0.017), while uPA levels showed no significant association with overall survival. Relating the levels of PAI-1 to other prognostic factors such as stage and age, no significant correlations were found. The prognostic impact of uPA and PAI-1 were investigated together with other prognostic factors in Cox multivariate analysis. PAI-1 was found to be an independent prognostic variable for survival, the relative risks being 1.5 (low versus medium PAI-1 values (95% confidence interval, 1.2–1.8) and 2.2 flow versus high (95% confidence interval, 1.8–2.6)). In patients with stage I disease (69 patients) high levels of PAI-1 were significantly associated with poor prognosis compared to low levels (P = 0.037). These data indicate that PAI-1 is a potentially important prognostic factor in pulmonary adenocarcinoma and may as such be used to select patients with low stage and poor prognosis for adjuvant therapy subsequent to complete surgical resection.

Footnotes

  • ↵1 This study was supported by the Danish Cancer Society.

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

  • Received July 17, 1993.
  • Accepted November 1, 1993.
  • ©1994 American Association for Cancer Research.
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January 1994
Volume 54, Issue 1
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Urokinase and Plasminogen Activator Inhibitor Type 1 in Pulmonary Adenocarcinoma
Helle Pedersen, Jan Grøndahl-Hansen, Dorte Francis, Kell Østerlind, Heine Høi Hansen, Keld Danø and Nils Brünner
Cancer Res January 1 1994 (54) (1) 120-123;

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Urokinase and Plasminogen Activator Inhibitor Type 1 in Pulmonary Adenocarcinoma
Helle Pedersen, Jan Grøndahl-Hansen, Dorte Francis, Kell Østerlind, Heine Høi Hansen, Keld Danø and Nils Brünner
Cancer Res January 1 1994 (54) (1) 120-123;
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