Book of abstract 2008

Plasma MMP1, MMP8 and MMP13 expression in breast cancer:
protective role of MMP8 against lymph node metastasis
Julie Decock1 ,2, Wouter Hendrickx1 ,3, Ulla Vanleeuw1, Vanya Van Belle4, Sabine Van
Huffel4, Marie Rose Christiaens3, Dylan Edwards2, Shu Ye5, Robert Paridaens1 ,3
1Laboratory for Experimental Oncology (LEO), K.U.Leuven, University Hospitals Leuven, Leuven,
Belgium; 2Biomedical Research Centre, School of Biological Sciences, University of East Anglia, Norwich,
UK; 3Multidisciplinary Breast Centre (MBC), University Hospitals Leuven, Leuven, Belgium; 4Dept. of
Electrical Engineering (ESAT), Division SCD, K.U.Leuven, Leuven, Belgium; 5William Harvey Research
Institute, Barts and The London Queen Mary School of Medicine and Dentistry, University of London,
London, UK
Elevated levels of matrix metalloproteinases have been found to associate with poor
prognosis in various carcinomas. This study aimed at evaluating plasma levels of MMP1,
MMP8 and MMP13 as diagnostic and prognostic markers of breast cancer.
A total of 208 breast cancer patients, of which 21 with inflammatory breast cancer, and 42
healthy controls were included in the study. Plasma levels of MMP1, MMP8 and MMP13
were measured using ELISA and correlated with clinicopathological characteristics.
Median plasma MMP1 levels were significantly higher in controls (3.45 ng/ml) than in
breast cancer patients (2.01 ng/ml), while no difference was found in MMP8 levels (10.74
vs. 10.49 ng/ml). ROC curve analysis revealed an AUC of 0.67, a sensitivity of 80% and
specificity of 24% at a cut-off value of 4.24 ng/ml. Plasma MMP13 levels could not be
detected. No correlation was found between MMP1 and MMP8 levels. We found a trend
of lower MMP1 levels with increasing tumour size (p=0.07); and of higher MMP8 levels
with premenopausal status (p=0.06) and NPI (p=0.04). A 2-fold decrease in MMP1
(p=0.02) and MMP8 (p=0.007) levels was observed in inflammatory breast cancer
patients. Intriguingly, plasma MMP8 levels were positively associated with lymph node
involvement but showed a negative correlation with the risk of distant metastasis. Both
healthy controls and patients without lymph node involvement (pN0) had lower MMP8
levels than patients with moderate lymph node involvement (pN1, pN2) (p=0.001), and
showed a trend for higher
l5
MMP8 levels as compared to those in patients with extensive
lymph node involvement (pN3) and a strong predisposition to distant metastasis (p=0.11).
Based on the hypothesis that blood and tissue protein levels are in reverse association,
these results suggest that MMP8 in the tumour may have a protective effect against lymph
node metastasis.
In summary, we observed differences in MMP1 and MMP8 plasma levels between healthy
controls and breast cancer patients as well as between breast cancer patients. Interestingly,
our results suggest that MMP8 may affect the metastatic behaviour of breast cancer cells
through protection against lymph node metastasis, underlining the importance of antitarget
identification in drug development.
This work is supported by the Vlaamse Liga tegen Kanker and the European Union Framework 6 LSHC-
CT-2003-503297.
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