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. 2006;8(3):R28.
doi: 10.1186/bcr1503. Epub 2006 Jun 15.

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

Bernard Têtu  1 , Jacques Brisson, Chang Shu Wang, Hélène Lapointe, Geneviève Beaudry, Caty Blanchette, Dominique Trudel
Affiliations

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

Bernard Têtu et al. Breast Cancer Res. 2006.

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 (> or = 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.

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Figures

Figure 1
Figure 1
Expression of matrix metalloproteinase (MMP)-2, MMP-14 and tissue inhibitor of metalloproteases (TIMP)-2 in stromal and cancer cells. (a) MMP-2 expression by stromal cells (in situ hybridization, × 200); (b) MMP-14 expression by stromal cells (in situ hybridization, × 200); (c) TIMP-2 expression by stromal cells (in situ hybridization, × 200); (d) TIMP-2 expression by cancer cells (in situ hybridization, × 200). Scale bar = 200 microns. C, cancer cells; S, stromal cells.
Figure 2
Figure 2
Overall survival for matrix metalloproteinase (MMP)-2, MMP-14 and tissue inhibitor of metalloproteases (TIMP)-2 expression by stromal and cancer cells. Overall survival curves for: (a) matrix metalloproteinase (MMP)-2 expressed by stromal cells; (b) MMP-14 expressed by stromal cells; (c) tissue inhibitor of metalloproteases (TIMP)-2 expressed by stromal cells; and (d) TIMP-2 expressed by cancer cells (p values obtained by the log-rank test).
Figure 3
Figure 3
Overall survival curves for: matrix metalloproteinase (MMP)-2, MMP-14 and stromal tissue inhibitor of metalloproteases (TIMP)-2 (p values obtained by the log-rank test).
See this image and copyright information in PMC

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