Measurement of the Uncomplexed Fraction of Tissue Inhibitor of Metalloproteinases-1 in the Prognostic Evaluation of Primary Breast Cancer Patients*
| Autor: | Vibeke Jensen, Anne Sofie Schrohl, Ib Jarle Christensen, Ulrik Lademann, Sidse Ørnbjerg Würtz, Nils Brünner, Henning T. Mouridsen |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Oncology
medicine.medical_specialty Multivariate analysis Denmark Breast Neoplasms Enzyme-Linked Immunosorbent Assay Disease Biochemistry Disease-Free Survival Analytical Chemistry Breast cancer Internal medicine medicine Humans Molecular Biology Total Tissue Survival analysis Retrospective Studies Tissue Inhibitor of Metalloproteinase-1 business.industry Proportional hazards model Hazard ratio Reproducibility of Results Prognosis medicine.disease Confidence interval Multivariate Analysis Immunology Regression Analysis Female Neoplasm Recurrence Local business |
| Zdroj: | Molecular & Cellular Proteomics. 4:483-491 |
| ISSN: | 1535-9476 |
| Popis: | Several studies have demonstrated an association between high tumor tissue levels of total tissue inhibitor of metalloproteinases-1 (TIMP-1) and a poor prognosis of primary breast cancer patients. In the present study we investigated whether measurements of the uncomplexed fraction of TIMP-1 added prognostic information to that already obtained from total TIMP-1. We measured the uncomplexed fraction of TIMP-1, using a thoroughly validated ELISA specific for this fraction, in 341 tumor tissue extracts obtained from patients with primary breast cancer. These measurements were related to previously performed measurements of total TIMP-1 as well as to patient outcome. The observation time was 8.3 years (range, 7.3-11.3 years). During this period 136 patients died, and 153 patients experienced recurrence of disease. Cox regression analysis of recurrence-free survival (RFS) suggested that a score based on both uncomplexed and total TIMP-1, reflecting the tumor level of TIMP-1/MMP complexes, would be a more precise estimate of prognosis than total TIMP-1 alone. Univariate survival analysis showed a highly significant relationship between high values of the score and poor outcomes for RFS (p = 0.0002; hazard ratio = 2.7; 95% confidence interval, 1.5-4.8). Similar results were found for overall survival (p = 0.0001; hazard ratio = 3.3; 95% confidence interval, 1.8-6.3). Multivariate analysis of RFS and overall survival demonstrated that the score was significant including the classical prognostic factors used in breast cancer (p < 0.0001). The present study raises the hypothesis that it is the tumor level of TIMP-1/MMP complexes (i.e. activated matrix metalloproteinases) rather than TIMP-1 itself that determines prognosis, supporting the use of the combined score and not only total TIMP-1 in stratification of breast cancer patients. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|