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The prognostic value of polymorphonuclear leukocyte elastase in patients with primary breast cancer.
Cancer Res. 2003 Jan 15; 63(2):337-41.CR

Abstract

A variety of serine proteases, including urokinase-type plasminogen activator (uPA), plasmin,and polymorphonuclear leukocyte elastase (PMN-E), have been implicated in the processes of tumor cell invasion and metastasis. Besides degrading of matrix proteins, PMN-E has been shown to be able to cleave and inactivate plasminogen activator inhibitor-1 (PAI-1), the main inhibitor of uPA, and alpha2-antiplasmin, the natural inhibitor of plasmin, thus enabling an uncontrolled matrix degradation by the fibrinolytic enzymes. Because only limited data are available on a relationship between the tumor level of PMN-E and prognosis in primary breast cancer patients, in the present study we have measured with an ELISA the levels of PMN-E (in complex with alpha1-proteinase inhibitor) in cytosolic extracts of 1143 primary breast tumors. Levels of complexed PMN-E have been correlated with the lengths of metastasis-free survival (MFS), relapse-free survival, and overall survival, and a comparison was made with data previously obtained for uPA and PAI-1. Our results show that patients with a high PMN-E level in their primary tumor had a rapid relapse and an early death compared with patients with a low tumor level of PMN-E. This held true for node-negative and node-positive subgroups of patients as well. The relationship of PMN-E with a poor prognosis was especially obvious during short-term follow-up (0-60 months). In Cox multivariate regression analysis, corrected for the traditional prognostic factors, PMN-E was an independent prognostic factor, and high levels of PMN-E were associated with a poor MFS [hazard ratio (HR), 1.63; 95% confidence interval (CI), 1.23-2.16; P < 0.001], relapse-free survival (HR, 1.45; 95% CI, 1.10-1.89; P = 0.01), and overall survival (HR, 1.64; 95% CI, 1.20-2.23; P = 0.003). Furthermore, in all three multivariate models, PMN-E still added significantly to the model after the additional inclusion of the uPA. PMN-E was an independent prognostic factor for MFS even in the multivariate analysis including the traditional clinical prognostic factors and the strong established biochemical prognostic factors uPA and PAI-1. Our present study suggests that PMN-E is associated with breast cancer metastasis, and knowledge of the tumor PMN-E status might be helpful in selecting the appropriate individualized (adjuvant) treatment for patients with breast cancer.

Authors+Show Affiliations

Erasmus MC-Daniel den Hoed, Department of Medical Oncology, 3000 DR Rotterdam, The Netherlands. Foekens@bidh.azr.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12543785

Citation

Foekens, John A., et al. "The Prognostic Value of Polymorphonuclear Leukocyte Elastase in Patients With Primary Breast Cancer." Cancer Research, vol. 63, no. 2, 2003, pp. 337-41.
Foekens JA, Ries C, Look MP, et al. The prognostic value of polymorphonuclear leukocyte elastase in patients with primary breast cancer. Cancer Res. 2003;63(2):337-41.
Foekens, J. A., Ries, C., Look, M. P., Gippner-Steppert, C., Klijn, J. G., & Jochum, M. (2003). The prognostic value of polymorphonuclear leukocyte elastase in patients with primary breast cancer. Cancer Research, 63(2), 337-41.
Foekens JA, et al. The Prognostic Value of Polymorphonuclear Leukocyte Elastase in Patients With Primary Breast Cancer. Cancer Res. 2003 Jan 15;63(2):337-41. PubMed PMID: 12543785.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The prognostic value of polymorphonuclear leukocyte elastase in patients with primary breast cancer. AU - Foekens,John A, AU - Ries,Christian, AU - Look,Maxime P, AU - Gippner-Steppert,Cornelia, AU - Klijn,Jan G M, AU - Jochum,Marianne, PY - 2003/1/25/pubmed PY - 2003/3/14/medline PY - 2003/1/25/entrez SP - 337 EP - 41 JF - Cancer research JO - Cancer Res VL - 63 IS - 2 N2 - A variety of serine proteases, including urokinase-type plasminogen activator (uPA), plasmin,and polymorphonuclear leukocyte elastase (PMN-E), have been implicated in the processes of tumor cell invasion and metastasis. Besides degrading of matrix proteins, PMN-E has been shown to be able to cleave and inactivate plasminogen activator inhibitor-1 (PAI-1), the main inhibitor of uPA, and alpha2-antiplasmin, the natural inhibitor of plasmin, thus enabling an uncontrolled matrix degradation by the fibrinolytic enzymes. Because only limited data are available on a relationship between the tumor level of PMN-E and prognosis in primary breast cancer patients, in the present study we have measured with an ELISA the levels of PMN-E (in complex with alpha1-proteinase inhibitor) in cytosolic extracts of 1143 primary breast tumors. Levels of complexed PMN-E have been correlated with the lengths of metastasis-free survival (MFS), relapse-free survival, and overall survival, and a comparison was made with data previously obtained for uPA and PAI-1. Our results show that patients with a high PMN-E level in their primary tumor had a rapid relapse and an early death compared with patients with a low tumor level of PMN-E. This held true for node-negative and node-positive subgroups of patients as well. The relationship of PMN-E with a poor prognosis was especially obvious during short-term follow-up (0-60 months). In Cox multivariate regression analysis, corrected for the traditional prognostic factors, PMN-E was an independent prognostic factor, and high levels of PMN-E were associated with a poor MFS [hazard ratio (HR), 1.63; 95% confidence interval (CI), 1.23-2.16; P < 0.001], relapse-free survival (HR, 1.45; 95% CI, 1.10-1.89; P = 0.01), and overall survival (HR, 1.64; 95% CI, 1.20-2.23; P = 0.003). Furthermore, in all three multivariate models, PMN-E still added significantly to the model after the additional inclusion of the uPA. PMN-E was an independent prognostic factor for MFS even in the multivariate analysis including the traditional clinical prognostic factors and the strong established biochemical prognostic factors uPA and PAI-1. Our present study suggests that PMN-E is associated with breast cancer metastasis, and knowledge of the tumor PMN-E status might be helpful in selecting the appropriate individualized (adjuvant) treatment for patients with breast cancer. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/12543785/The_prognostic_value_of_polymorphonuclear_leukocyte_elastase_in_patients_with_primary_breast_cancer_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=12543785 DB - PRIME DP - Unbound Medicine ER -