Invasion factors uPA/PAI-1 and HER2 status provide independent and complementary information on patient outcome in node-negative breast cancer.

Abstract

PURPOSE:

The independent clinical relevance of invasion factors urokinase-type plasminogen activator (uPA)/PAI-1 and HER2 status was evaluated in lymph node-negative breast cancer patients (N = 118) without adjuvant systemic therapy after long-term follow-up of more than 10 years (median, 126 months).

PATIENTS AND METHODS:

Levels of uPA and its inhibitor PAI-1 were prospectively measured by enzyme-linked immunosorbent assay in primary tumor tissue extracts. HER2 gene amplification (HER2_AMP) was evaluated by fluorescence in situ hybridization (FISH; Ventana Medical Systems HER-2/neu probe; Tucson, AZ), and HER2 protein overexpression (HER2_EXP) was evaluated by immunohistochemistry (IHC; Oncogene Science antibody Ab-3; Cambridge, MA) on parallel-cut formalin-fixed paraffin-embedded tissue sections.

RESULTS:

uPA/PAI-1 was high (either one or both factors were high) in 44% of the tumors. HER2_AMP was detected by FISH in 33% of the patients, and HER2_EXP was found by IHC in 44% of the patients. In a multivariate analysis of established and tumor-biologic prognostic factors, uPA/PAI-1 was the only independent prognostic factor for disease-free survival ([DFS]; P <.001; relative risk [RR], 8.3; 95% confidence interval [CI], 3.4 to 20.4). Although HER2_AMP and HER2_EXP did not reach significance for DFS, they were significant for overall survival (OS), even in multivariate analysis (HER2_AMP: P =.004; RR, 3.7; 95% CI, 1.5 to 9.2; HER2_EXP: P =.009; RR, 3.4; 95% CI, 1.4 to 8.7).

CONCLUSION:

After long-term follow-up, uPA/PAI-1 levels in primary tumor tissue reliably and strongly indicate an aggressive course of disease in lymph node-negative breast cancer independent of HER2 status. The particular prognostic effect of HER2 status on OS may reflect its ability to predict resistance to systemic therapy.

• Authors: Iris Zemzoum, Ronald E Kates, Jeffrey S Ross, Peer Dettmar, Moshumi Dutta, Cordula Henrichs, Suna Yurdseven, Heinz Höfler, Marion Kiechle, Manfred Schmitt, Nadia Harbeck
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 21 Issue 6 Pg. 1022-8 (Mar 15 2003) ISSN: 0732-183X [Print] United States
• PMID: 12637466 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Plasminogen Activator Inhibitor 1
• Receptor, ErbB-2
• Urokinase-Type Plasminogen Activator

Topics

• Adult
• Aged
• Analysis of Variance
• Biomarkers, Tumor (analysis, immunology)
• Breast Neoplasms (chemistry, mortality, pathology)
• Disease-Free Survival
• Female
• Follow-Up Studies
• Humans
• Immunohistochemistry
• In Situ Hybridization, Fluorescence
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Staging
• Plasminogen Activator Inhibitor 1 (analysis, immunology)
• Predictive Value of Tests
• Prognosis
• Receptor, ErbB-2 (analysis)
• Sensitivity and Specificity
• Survival Analysis
• Up-Regulation
• Urokinase-Type Plasminogen Activator (analysis, immunology)