Regular Article

British Journal of Cancer (2001) 85, 85–92. doi:10.1054/bjoc.2001.1867 www.bjcancer.com
Published online 3 July 2001

Prognostic impact of urokinase-type plasminogen activator receptor (uPAR) in cytosols and pellet extracts derived from primary breast tumours

J H de Witte1, J A Foekens2, N Brünner3, J J T M Heuvel1, ThH van Tienoven1, M P Look2, J G M Klijn2, A Geurts-Moespot1, N Grebenchtchikov1, ThJ Benraad1 and C G J Sweep1

  1. 1Department of Chemical Endocrinology, University Medical Centre Nijmegen, Nijmegen, The Netherlands
  2. 2Division of Endocrine Oncology (Department of Medical Oncology), Rotterdam Cancer Institute (Daniel den Hoed Kliniek) and University Hospital Rotterdam, Rotterdam, The Netherlands
  3. 3The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark

Received 12 December 2000; Revised 19 March 2001; Accepted 27 March 2001.

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Abstract

Using a previously developed enzyme-linked immunosorbent assay (ELISA), the levels of the receptor for urokinase-type plasminogen activator (uPAR) were determined in cytosols and corresponding membrane pellets derived from 878 primary breast tumours. The levels of uPAR in the pellet extracts were more than 3-fold higher than those measured in the cytosols (P< 0.001). Moreover, the uPAR levels in the two types of extracts were weakly, though significantly, correlated with each other (rS= 0.20, P< 0.001). In Cox univariate analysis, high cytosolic levels of uPAR were significantly associated with reduced overall survival (OS) and relapse-free survival (RFS). The levels of uPAR in pellet extracts appeared not to be related with patient survival. In multivariate analysis, elevated levels of uPAR measured in cytosols and pellet extracts were found to be independent predictors of poor OS, not RFS. The prediction of poor prognosis on the basis of high uPAR levels emphasizes its important role in plasmin-mediated degradation of extracellular matrix proteins during cancer invasion and metastasis. © 2001 Cancer Research Campaign http://www.bjcancer.com

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