This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Foekens, J. A. Articles by Jochum, M. Search for Related Content PubMed PubMed Citation Articles by Foekens, J. A. Articles by Jochum, M.

The Prognostic Value of Polymorphonuclear Leukocyte Elastase in Patients with Primary Breast Cancer¹

Erasmus MC-Daniel den Hoed, Department of Medical Oncology, 3000 DR Rotterdam, the Netherlands [J. A. F., M. P. L., J. G. M. K.], and Division of Clinical Biochemistry, Department of Surgery, Ludwig-Maximilians-University, D-80336 Munich, Germany [C. R., C. G-S., M. J.]

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 ₂-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 ₁-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.

This article has been cited by other articles:

				T. Yokota, T. Bui, Y. Liu, M. Yi, K. K. Hunt, and K. Keyomarsi Differential Regulation of Elafin in Normal and Tumor-Derived Mammary Epithelial Cells Is Mediated by CCAAT/Enhancer Binding Protein Cancer Res., December 1, 2007; 67(23): 11272 - 11283. [Abstract] [Full Text] [PDF]

				J. E. De Larco, B. R. K. Wuertz, and L. T. Furcht The Potential Role of Neutrophils in Promoting the Metastatic Phenotype of Tumors Releasing Interleukin-8 Clin. Cancer Res., August 1, 2004; 10(15): 4895 - 4900. [Abstract] [Full Text] [PDF]

				M. E. M.-v. Gelder, M. P. Look, H. A. Peters, M. Schmitt, N. Brunner, N. Harbeck, J. G. M. Klijn, and J. A. Foekens Urokinase-Type Plasminogen Activator System in Breast Cancer: Association with Tamoxifen Therapy in Recurrent Disease Cancer Res., July 1, 2004; 64(13): 4563 - 4568. [Abstract] [Full Text] [PDF]

				A. Scorilas, C. A. Borgono, N. Harbeck, J. Dorn, B. Schmalfeldt, M. Schmitt, and E. P. Diamandis Human Kallikrein 13 Protein in Ovarian Cancer Cytosols: A New Favorable Prognostic Marker J. Clin. Oncol., February 15, 2004; 22(4): 678 - 685. [Abstract] [Full Text] [PDF]

				P. A. Davol, R. Bagdasaryan, G. J. Elfenbein, A. L. Maizel, and A. R. Frackelton Jr. Shc Proteins Are Strong, Independent Prognostic Markers for Both Node-Negative and Node-Positive Primary Breast Cancer Cancer Res., October 15, 2003; 63(20): 6772 - 6783. [Abstract] [Full Text] [PDF]