PMID- 11352966
OWN - NLM
STAT- MEDLINE
DCOM- 20010607
LR  - 20170210
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 19
IP  - 10
DP  - 2001 May 15
TI  - Functional evaluation of plasmin formation in primary breast cancer.
PG  - 2731-8
AB  - PURPOSE: Plasmin generation is controlled by the plasminogen activators 
      (PA)/plasmin system, which comprises proteases (urokinase-type PA [uPA] and 
      tissue-type PA [tPA]) and antiproteases (PA inhibitors, PAI-1 and PAI-2). The 
      tumoral content of uPA and PAI-1 has been shown to carry prognostic value in 
      breast cancer; however, because most assays used so far have relied on 
      immunometric determinations, we have explored the enzymatic activities governing 
      plasmin formation in breast cancer specimens. PATIENTS AND METHODS: We applied 
      semiquantitative histochemical zymography to 201 primary breast cancer tissue 
      sections. Enzymatic activities were correlated with histopathologic parameters 
      and clinical outcome. The median follow-up was 91 months. RESULTS: A wide range 
      of PA-mediated catalytic activities was detected. The overall survival was 
      significantly worse for patients with tumors showing tPA in the lowest quartile 
      of activity (P =.003). The 5-year overall survival of patients with tPA activity 
      in the lowest quartile was 58% compared with 81% for patients with tPA value in 
      the other three quartiles. Tumor size, axillary lymph node metastasis, histologic 
      grade, lymphovascular infiltration, TP53 mutation, and tPA activity were all 
      major risk factors in univariate analysis. tPA activity was an independent 
      prognostic factor in a multivariate Cox regression model, both in the whole 
      population (relative risk = 0.5, 95% confidence interval, 0.3 to 0.9; P =.02) and 
      in the node-negative subgroup (relative risk = 0.2, 95% confidence interval, 0.08 
      to 0.6; P =.004). CONCLUSION: By using a zymographic assay performed directly on 
      primary tumor tissue sections, we demonstrate that reduced tPA-mediated plasmin 
      production is an independent adverse prognostic factor in breast cancer.
FAU - Chappuis, P O
AU  - Chappuis PO
AD  - Division of Oncology, Department of Medicine, Hopitaux Universitaires, and 
      Medical University Centre, Geneva, Switzerland. pierr.chappuis@muhc.mcgill.ca
FAU - Dieterich, B
AU  - Dieterich B
FAU - Sciretta, V
AU  - Sciretta V
FAU - Lohse, C
AU  - Lohse C
FAU - Bonnefoi, H
AU  - Bonnefoi H
FAU - Remadi, S
AU  - Remadi S
FAU - Sappino, A P
AU  - Sappino AP
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 (Fibrinolytic Agents)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (Plasminogen Activator Inhibitor 2)
RN  - 0 (Serine Proteinase Inhibitors)
RN  - EC 3.4.21.68 (Tissue Plasminogen Activator)
RN  - EC 3.4.21.7 (Fibrinolysin)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
SB  - IM
MH  - Breast Neoplasms/enzymology/*metabolism/mortality/pathology
MH  - Female
MH  - Fibrinolysin/*biosynthesis
MH  - Fibrinolytic Agents/*metabolism
MH  - Humans
MH  - Middle Aged
MH  - Plasminogen Activator Inhibitor 1/metabolism
MH  - Plasminogen Activator Inhibitor 2/metabolism
MH  - Prognosis
MH  - Regression Analysis
MH  - Serine Proteinase Inhibitors/metabolism
MH  - Survival Rate
MH  - Tissue Plasminogen Activator/*metabolism
MH  - Urokinase-Type Plasminogen Activator/*metabolism
EDAT- 2001/05/16 10:00
MHDA- 2001/06/08 10:01
CRDT- 2001/05/16 10:00
PHST- 2001/05/16 10:00 [pubmed]
PHST- 2001/06/08 10:01 [medline]
PHST- 2001/05/16 10:00 [entrez]
AID - 10.1200/JCO.2001.19.10.2731 [doi]
PST - ppublish
SO  - J Clin Oncol. 2001 May 15;19(10):2731-8. doi: 10.1200/JCO.2001.19.10.2731.