Tags

Type your tag names separated by a space and hit enter

Complex of urokinase-type plasminogen activator with its type 1 inhibitor predicts poor outcome in 576 patients with lymph node-negative breast carcinoma.
Cancer. 2004 Aug 01; 101(3):486-94.C

Abstract

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.

Authors+Show Affiliations

Department of Chemical Endocrinology, University Medical Centre Nijmegen, Nijmegen, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15274061

Citation

Manders, Peggy, et al. "Complex of Urokinase-type Plasminogen Activator With Its Type 1 Inhibitor Predicts Poor Outcome in 576 Patients With Lymph Node-negative Breast Carcinoma." Cancer, vol. 101, no. 3, 2004, pp. 486-94.
Manders P, Tjan-Heijnen VC, Span PN, et al. Complex of urokinase-type plasminogen activator with its type 1 inhibitor predicts poor outcome in 576 patients with lymph node-negative breast carcinoma. Cancer. 2004;101(3):486-94.
Manders, P., Tjan-Heijnen, V. C., Span, P. N., Grebenchtchikov, N., Geurts-Moespot, A., van Tienoven, D. T., Beex, L. V., & Sweep, F. C. (2004). Complex of urokinase-type plasminogen activator with its type 1 inhibitor predicts poor outcome in 576 patients with lymph node-negative breast carcinoma. Cancer, 101(3), 486-94.
Manders P, et al. Complex of Urokinase-type Plasminogen Activator With Its Type 1 Inhibitor Predicts Poor Outcome in 576 Patients With Lymph Node-negative Breast Carcinoma. Cancer. 2004 Aug 1;101(3):486-94. PubMed PMID: 15274061.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Complex of urokinase-type plasminogen activator with its type 1 inhibitor predicts poor outcome in 576 patients with lymph node-negative breast carcinoma. AU - Manders,Peggy, AU - Tjan-Heijnen,Vivianne C G, AU - Span,Paul N, AU - Grebenchtchikov,Nicolai, AU - Geurts-Moespot,Anneke, AU - van Tienoven,Doorlène T H, AU - Beex,Louk V A M, AU - Sweep,Fred C G J, PY - 2004/7/27/pubmed PY - 2004/8/18/medline PY - 2004/7/27/entrez SP - 486 EP - 94 JF - Cancer JO - Cancer VL - 101 IS - 3 N2 - 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. SN - 0008-543X UR - https://www.unboundmedicine.com/medline/citation/15274061/Complex_of_urokinase_type_plasminogen_activator_with_its_type_1_inhibitor_predicts_poor_outcome_in_576_patients_with_lymph_node_negative_breast_carcinoma_ L2 - https://doi.org/10.1002/cncr.20374 DB - PRIME DP - Unbound Medicine ER -