Dissemination risk index based on plasminogen activator system components in primary breast cancer
| Autor: | Michèle Tubiana-Hulin, Kamel Hacène, Frédérique Spyratos, Jean Oglobine, Véronique Becette, Pierre-Marie Martin, Serge Lasry, Cécile Bouchet |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Oncology
Adult Cancer Research medicine.medical_specialty Mammary gland Breast Neoplasms Receptors Cell Surface Risk Assessment Metastasis chemistry.chemical_compound Internal medicine Plasminogen Activator Inhibitor 1 medicine Biomarkers Tumor Plasminogen Activator Inhibitor 2 Humans Aged Retrospective Studies Aged 80 and over Univariate analysis business.industry Proportional hazards model Middle Aged medicine.disease Prognosis Urokinase-Type Plasminogen Activator Urokinase receptor medicine.anatomical_structure Endocrinology chemistry Plasminogen activator inhibitor-1 Plasminogen activator inhibitor-2 Female business Plasminogen activator |
| Zdroj: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 17(10) |
| ISSN: | 0732-183X |
| Popis: | 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 × 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. |
| Databáze: | OpenAIRE |
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