This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bouchet, C. Articles by Spyratos, F. Search for Related Content PubMed PubMed Citation Articles by Bouchet, C. Articles by Spyratos, F. Social Bookmarking                            What's this?

Dissemination Risk Index Based on Plasminogen Activator System Components in Primary Breast Cancer

From the Département de Biologie, Département de Statistiques Médicales, Département d'Anatomie-Pathologique, Département de Médecine, and Département de Chirurgie, Centre René Huguenin, St-Cloud; and Laboratoire de Transfert, Assistance Publique-Hôpitaux de Marseille, Marseille, France.

Address reprint requests to Frédérique Spyratos, Laboratoire de Biologie Tissulaire, Centre René Huguenin, 35 Rue Dailly, 92211 St-Cloud, France; email spyratos{at}calva.net

PURPOSE: To study interactions between disease-free survival (DFS) and four components of the plasminogen activator system: urokinase-type plasminogen activator (uPA), its two inhibitors (PAI-1 and PAI-2), and its membrane receptor uPAR.

PATIENTS AND METHODS: We conducted a retrospective study of 499 primary breast cancer patients (median follow-up, 6 years). uPA, PAI-1, and PAI-2 were determined on cytosols and uPAR on solubilized pellets, using enzyme-linked immunoadsorbent assay kits (American Diagnostica, Greenwich, CT). Classical univariate and multivariate statistical methods were used together with multiple correspondence analysis to graphically examine interactions between the variables and outcome.

RESULTS: By univariate analysis, higher uPA and PAI-1 values were significantly related to shorter DFS (P = .002; P < .00002). PAI-2 was not significantly related to DFS, although patients with high and very low PAI-2 values had a longer DFS. Multiple correspondence analysis showed the parallel impact of uPA and PAI-1 on outcome, and the clearly different behavior of PAI-2 compared with PAI-1. The prognostic contribution of uPAR seemed weak by both methods. A dissemination risk index [uPA x PAI-1/(PAI-2 + 1)], taking into account the modulation of uPA proteolytic activity by the ratio of its two inhibitors, was then tested. Dissemination risk index was selected as an independent variable in the Cox model in the overall population (P < .000001) and in node-positive patients (P < .00001). It was the only variable selected in node-negative patients (P = .003).

CONCLUSION: A dissemination risk index determined on primary tumor and taking into account the different effects of PAI-1 and PAI-2 on uPA can be of major help in clinical management of breast cancer, particularly in node-negative patients.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				L. Harris, H. Fritsche, R. Mennel, L. Norton, P. Ravdin, S. Taube, M. R. Somerfield, D. F. Hayes, and R. C. Bast Jr American Society of Clinical Oncology 2007 Update of Recommendations for the Use of Tumor Markers in Breast Cancer J. Clin. Oncol., November 20, 2007; 25(33): 5287 - 5312. [Abstract] [Full Text] [PDF]

				E A Baker, T J Stephenson, M W R Reed, and N J Brown Expression of proteinases and inhibitors in human breast cancer progression and survival Mol. Pathol., October 1, 2002; 55(5): 300 - 304. [Abstract] [Full Text] [PDF]

				N. Harbeck, R. E. Kates, and M. Schmitt Clinical Relevance of Invasion Factors Urokinase-Type Plasminogen Activator and Plasminogen Activator Inhibitor Type 1 for Individualized Therapy Decisions in Primary Breast Cancer Is Greatest When Used in Combination J. Clin. Oncol., February 15, 2002; 20(4): 1000 - 1007. [Abstract] [Full Text] [PDF]

				M. P. Look, W. L. J. van Putten, M. J. Duffy, N. Harbeck, I. J. Christensen, C. Thomssen, R. Kates, F. Spyratos, M. Ferno, S. Eppenberger-Castori, et al. Pooled Analysis of Prognostic Impact of Urokinase-Type Plasminogen Activator and Its Inhibitor PAI-1 in 8377 Breast Cancer Patients J Natl Cancer Inst, January 16, 2002; 94(2): 116 - 128. [Abstract] [Full Text] [PDF]

				N. Harbeck, U. Alt, U. Berger, A. Kruger, C. Thomssen, F. Janicke, H. Hofler, R. E. Kates, and M. Schmitt Prognostic Impact of Proteolytic Factors (Urokinase-Type Plasminogen Activator, Plasminogen Activator Inhibitor 1, and Cathepsins B, D, and L) in Primary Breast Cancer Reflects Effects of Adjuvant Systemic Therapy Clin. Cancer Res., September 1, 2001; 7(9): 2757 - 2764. [Abstract] [Full Text] [PDF]

				M. S. Aapro Adjuvant Therapy of Primary Breast Cancer: A Review of Key Findings from the 7th International Conference, St. Gallen, February 2001 Oncologist, August 1, 2001; 6(4): 376 - 385. [Abstract] [Full Text] [PDF]

				P. O. Chappuis, B. Dieterich, V. Sciretta, C. Lohse, H. Bonnefoi, S. Remadi, and A.-P. Sappino Functional Evaluation of Plasmin Formation in Primary Breast Cancer J. Clin. Oncol., May 15, 2001; 19(10): 2731 - 2738. [Abstract] [Full Text] [PDF]

				N. C. Denko and A. J. Giaccia Tumor Hypoxia, the Physiological Link between Trousseau's Syndrome (Carcinoma-induced Coagulopathy) and Metastasis Cancer Res., February 1, 2001; 61(3): 795 - 798. [Full Text]

				J. A. Foekens, H. A. Peters, M. P. Look, H. Portengen, M. Schmitt, M. D. Kramer, N. Brunner, F. Janicke, M. E. M.-v. Gelder, S. C. Henzen-Logmans, et al. The Urokinase System of Plasminogen Activation and Prognosis in 2780 Breast Cancer Patients Cancer Res., February 1, 2000; 60(3): 636 - 643. [Abstract] [Full Text]