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Breast Cancer Research
Published in: Breast Cancer Research 3/2006

Open Access 01-06-2006 | Research article

The influence of MMP-14, TIMP-2 and MMP-2 expression on breast cancer prognosis

Authors: Bernard Têtu, Jacques Brisson, Chang Shu Wang, Hélène Lapointe, Geneviève Beaudry, Caty Blanchette, Dominique Trudel

Published in: Breast Cancer Research | Issue 3/2006

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Abstract

Introduction

Matrix metalloproteinase (MMP)-2 is very active at degrading extracellular matrix. It is under the influence of an activator, membrane type 1 MMP (MMP-14), and the tissue inhibitor of metalloproteases (TIMP)-2. We hypothesized that the individual expression of these three markers or their balance may help to predict breast cancer prognosis.

Methods

MMP-2, MMP-14 and TIMP-2 expression has been evaluated by 35S mRNA in situ hybridization on paraffin material of 539 breast cancers without distant metastasis at diagnosis and with a median follow-up of 9.2 years.

Results

MMP-2 and MMP-14 mRNA was detected primarily in reactive stromal cells whereas TIMP-2 mRNA was expressed by both stromal and cancer cells. Of the three molecules, an adjusted Cox model revealed that high MMP-14 mRNA (≥ 10% cells) alone predicted a significantly shorter overall survival (p = 0.031) when adjusted for clinical factors (tumor size and number of involved lymph nodes). Prognostic significance was lost when further adjusted for Her-2/neu and urokinase-type plasminogen activator (p = 0.284). Furthermore, when all three components were analyzed together, the survival was worst for patients with high MMP-2/high MMP-14/low TIMP-2 (5 year survival = 60%) and best with low MMP-2/low MMP-14/high TIMP-2 (5 year survival = 74%), but the difference did not reach statistical significance (p = 0.3285).

Conclusion

Of the MMP-14/TIMP-2/MMP-2 complex, MMP-14 was the factor most significantly associated with the outcome of breast cancer and was an independent factor of poor overall survival when adjusted for clinical prognostic factors, but not for certain ancillary markers.
Appendix
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Metadata
Title
The influence of MMP-14, TIMP-2 and MMP-2 expression on breast cancer prognosis
Authors
Bernard Têtu
Jacques Brisson
Chang Shu Wang
Hélène Lapointe
Geneviève Beaudry
Caty Blanchette
Dominique Trudel
Publication date
01-06-2006
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 3/2006
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr1503

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