prognostic significance of urokinase type plasminogen activator upa and plasminogen activator inhibitor pai 1 in patients with primary invasive ductal breast carcinoma a 7 5 year follow up study

• DOI: 10.1700/950.10409
• Publication Date: 2011-07-01
• Authors: Sanda Jelisavac-Ć...; Damir Vrbanec; Jasminka Jakić-Ra...; Maja Sirotković-S...; Aana Kulić; Zdenko Kovač
• Keywords: Adult; Breast Neoplasms; Enzyme-Linked Immunosorbent Assay; Kaplan-Meier Estimate; 03 medical and health sciences; 0302 clinical medicine; Predictive Value of Tests; Plasminogen Activator Inhibitor 1; Biomarkers, Tumor; Humans; Aged; Analysis of Variance; Carcinoma, Ductal, Breast; Middle Aged; Prognosis; Urokinase-Type Plasminogen Activator; 3. Good health; Receptors, Estrogen; Lymphatic Metastasis; uPA ; PAI-1 ; breast cancer; Female; Neoplasm Grading; Receptors, Progesterone; Follow-Up Studies

Aims and background Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor (PAI-1) are key molecules in pericellular proteolysis, a process that plays an important role in tumor invasion and metastasis. In the current study we investigated the prognostic significance of uPA and PAI-1 in primary invasive breast cancer. Methods and study design uPA and PAI-1 antigen levels were determined by enzyme-linked immunosorbent assay in cytosols of 177 invasive ductal carcinoma specimens. The prognostic significance of uPA and PAI-1 was assessed for overall survival. The median follow-up time was 90 months. Results In univariate analysis, both uPA (third versus first tertile range of values; P = 0.02; HR = 2.08) and PAI-1 (third versus first tertile; P = 0.0007; HR = 3.1) were significant prognostic markers for overall survival. In multivariate analysis only nodal status (N2 vs N0; P = 0.0001; HR = 3.94) and PAI-1 (third versus first tertile; P = 0.004; HR = 3.05) remained significant independent prognostic factors. Both uPA and PAI-1 were correlated with established prognostic markers including histological grade, tumor size and Nottingham index. Conclusion Our study with a 7.5-year follow-up confirmed the relation between elevated uPA and PAI-1 values and an aggressive course of invasive breast cancer. The prognostic significance of PAI-1 as an independent marker was proved for the overall group of breast cancer patients and the subgroup of node-positive patients.