Complex of urokinase-type plasminogen activator with its type 1 inhibitor predicts poor outcome in 576 patients with lymph node–negative breast carcinoma
✍ Scribed by Peggy Manders; Vivianne C. G. Tjan-Heijnen; Paul N. Span; Nicolai Grebenchtchikov; Anneke Geurts-Moespot; Doorlène T. H. van Tienoven; Louk V. A. M. Beex; Fred C. G. J. Sweep
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 128 KB
- Volume
- 101
- Category
- Article
- ISSN
- 0008-543X
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✦ Synopsis
Background:
The ability of a solid tumor to grow and metastasize has a significant dependence on protease systems, such as the plasminogen activation system. the plasminogen activation system includes the urokinase-type plasminogen activator (upa) and plasminogen activator inhibitor type 1 (pai-1), among other molecules. both upa and pai-1 are established prognostic factors for patients with breast carcinoma. in the current study, the authors investigated whether the complex of upa with pai-1 is also associated with the natural course of this malignancy.
Methods:
Cytosolic levels of upa, pai-1, and the upa:pai-1 complex were measured in tumor tissue from 576 patients with lymph node-negative invasive breast carcinoma using quantitative enzyme-linked immunosorbent assays. patients did not receive adjuvant systemic therapy, and the median follow-up duration was 61 months (range, 2-187 months) after primary diagnosis. correlations with well known clinicopathologic factors were assessed, and univariate and multivariate survival analyses were performed.
Results:
Upa:pai-1 complex levels were positively associated with adverse histologic grade and inversely correlated with estrogen and progesterone receptor status. on univariate analysis, increased levels of the upa:pai-1 complex were found to be associated with reduced recurrence-free survival (rfs) and overall survival (os) rates. on multivariate analysis, upa:pai-1 complex levels were found to be an independent predictor of os (p = 0.039), but not rfs (p = 0.240). when upa and pai-1 levels were not included in the multivariate analysis, upa:pai-1 complex levels became a significant predictor of both rfs and os (p = 0.029 and p = 0.007, respectively).
Conclusions:
The results of the current study demonstrate that upa:pai-1 complex levels have prognostic value on univariate analysis. in addition, increased upa:pai-1 complex levels were significantly associated with poor os on multivariate analysis. increased upa:pai-1 complex levels were also significantly associated with reduced rfs rates after the exclusion of upa and pai-1 levels from the multivariate analysis model.