PMID- 12637466
OWN - NLM
STAT- MEDLINE
DCOM- 20030410
LR  - 20161102
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 21
IP  - 6
DP  - 2003 Mar 15
TI  - Invasion factors uPA/PAI-1 and HER2 status provide independent and complementary 
      information on patient outcome in node-negative breast cancer.
PG  - 1022-8
AB  - 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.
FAU - Zemzoum, Iris
AU  - Zemzoum I
AD  - Frauenklinik and Institut fur Allgemeine Pathologie und Pathologische Anatomie, 
      Technische Universitat, and Gemeinschaftspraxis Lachnerstrasse 2 fur Pathologie 
      und Zytologie, Munchen, Germany.
FAU - Kates, Ronald E
AU  - Kates RE
FAU - Ross, Jeffrey S
AU  - Ross JS
FAU - Dettmar, Peer
AU  - Dettmar P
FAU - Dutta, Moshumi
AU  - Dutta M
FAU - Henrichs, Cordula
AU  - Henrichs C
FAU - Yurdseven, Suna
AU  - Yurdseven S
FAU - Hofler, Heinz
AU  - Hofler H
FAU - Kiechle, Marion
AU  - Kiechle M
FAU - Schmitt, Manfred
AU  - Schmitt M
FAU - Harbeck, Nadia
AU  - Harbeck N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Analysis of Variance
MH  - Biomarkers, Tumor/*analysis/immunology
MH  - Breast Neoplasms/*chemistry/mortality/pathology
MH  - Disease-Free Survival
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Middle Aged
MH  - Neoplasm Invasiveness
MH  - Neoplasm Staging
MH  - Plasminogen Activator Inhibitor 1/*analysis/immunology
MH  - Predictive Value of Tests
MH  - Prognosis
MH  - Receptor, ErbB-2/*analysis
MH  - Sensitivity and Specificity
MH  - Survival Analysis
MH  - Up-Regulation
MH  - Urokinase-Type Plasminogen Activator/*analysis/immunology
EDAT- 2003/03/15 04:00
MHDA- 2003/04/11 05:00
CRDT- 2003/03/15 04:00
PHST- 2003/03/15 04:00 [pubmed]
PHST- 2003/04/11 05:00 [medline]
PHST- 2003/03/15 04:00 [entrez]
AID - 10.1200/JCO.2003.04.170 [doi]
PST - ppublish
SO  - J Clin Oncol. 2003 Mar 15;21(6):1022-8. doi: 10.1200/JCO.2003.04.170.