Expression and prognostic value of plasminogen activator inhibitor type 1 in node-negative breast cancer

2008 ◽  
Vol 7 (6) ◽  
pp. 339-343 ◽  
Author(s):  
Bin Wang ◽  
Ning Wang ◽  
Chunyan Xue ◽  
Bin Jiang ◽  
Yajie Wang



1996 ◽  
Vol 32 ◽  
pp. S20
Author(s):  
Mårten Fernö ◽  
Pär-Ola Bendahl ◽  
Nils Brünner ◽  
Eva Långstróm ◽  
Håkan Olsson ◽  
...  


2002 ◽  
Vol 20 (4) ◽  
pp. 1000-1007 ◽  
Author(s):  
Nadia Harbeck ◽  
Ronald E. Kates ◽  
Manfred Schmitt

PURPOSE: A strong prognostic impact of urokinase-type plasminogen activator (uPA) and its inhibitor and plasminogen activator inhibitor type 1 (PAI-1) as individual factors is well established in breast cancer. The improvement in clinical risk assessment gained by combining these factors is evaluated here. PATIENTS AND METHODS: uPA and PAI-1 levels were prospectively measured by enzyme-linked immunosorbent assay in tumor tissue extracts of 761 patients with primary breast cancer. RESULTS: In the clinically important subgroup of node-negative patients without adjuvant systemic therapy (n = 269; median follow-up, 60 months), the clinical value of testing both uPA and PAI-1 is demonstrated. The criterion either or both high identifies with high sensitivity the patients at high relapse risk while keeping more than half in the low-risk group. uPA/PAI-1 is the strongest predictor of disease-free survival and overall survival; patients with high uPA/PAI-1 have an increased relapse risk (P < .001; relative risk, 4.8; 95% confidence interval [CI], 2.5 to 9.1), in particular for early relapse. Even within risk groups stratified by established criteria (nodal or menopausal status, tumor size, grade, or steroid hormone receptors), uPA/PAI-1 provides significant risk group discrimination. In the whole collective, the significant interaction between uPA/PAI-1 and adjuvant systemic therapy suggests a benefit from adjuvant therapy in high-risk patients as defined by uPA/PAI-1. CONCLUSION: The clinical relevance of the two tumor-invasion factors uPA and PAI-1 is greatest when they are used in combination. The particular combination of uPA and PAI-1 (both low v either or both high) is superior to either factor alone and supports risk-adapted individualized therapy decisions.



2002 ◽  
Vol 48 (8) ◽  
pp. 1288-1295 ◽  
Author(s):  
Remedios Castelló ◽  
Amparo Estellés ◽  
Carlos Vázquez ◽  
Cristina Falcó ◽  
Francisco España ◽  
...  

Abstract Background: The plasminogen activation system and matrix metalloproteinases (MMPs) play a key role in the degradation of basement membrane and extracellular matrix in tissue remodeling, cancer cell invasion, and metastasis. Methods: Quantitative real-time reverse-transcription-PCR (RT-PCR) assays were developed to quantify urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor type 1 (PAI-1), and tissue metalloproteinase inhibitor type 1 (TIMP-1) mRNA in 54 breast cancer tissues. Gene fragments were amplified in a LightCycler real-time PCR system using gene-specific primers and SYBR Green I. The results were normalized to β-actin mRNA. We also quantified antigen and functional concentrations of these components. Results: The intra- and interassay variabilities for mRNA quantification showed mean SDs for the crossing point of 0.12 and 0.15 cycles, respectively. PAI-1, uPA, and TIMP-1 mRNA and antigen concentrations and PAI-1 and uPA functional concentrations increased with tumor severity; the increase was statistically significant for PAI-1, uPA, and TIMP-1 mRNA and antigen concentrations and for uPA functional concentrations. Node-positive patients showed significantly higher PAI-1, uPA, and TIMP-1 mRNA and antigen concentrations than those who were node negative. Conclusions: Quantitative real-time RT-PCR is a highly sensitive, reproducible, and fast method for measuring gene expression of PAI-1, uPA, and TIMP-1 in breast cancer. These components may be involved in breast cancer development, and increased mRNA expression may be associated with a worse prognosis.



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