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Plasma Gelatinase Levels in Patients with Primary Breast Cancer in Relation to Axillary Lymph Node Status, Her2/neu Expression and other Clinicopathological Variables

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Abstract

Matrix metalloproteinases (MMPs), in particular the gelatinases MMP2 and MMP9, are important mediators of tumour invasion and metastasis. We examined whether plasma gelatinase levels could predict lymph node metastasis in breast cancer patients. Further, we investigated the relationship of plasma gelatinase levels with Her2/neu expression, recently acknowledged as an important prognostic factor for recurrence, and with various clinicopathological factors. Preoperative plasma samples from 81 breast cancer patients were collected. Total and active gelatinase levels were measured by enzyme immunoassays and activity assays, respectively. Neither total nor active plasma MMP2 levels correlated with nodal status or with any of the classical clinicopathological factors including histological tumour type, tumour size and grade and hormone receptor status. Patients with Her2/neu overexpressing tumours showed an increase of 27% (P=0.007) in plasma MMP2 activity, but not in total MMP2, compared with patients without overexpression. MMP9 levels, total and active, did not correlate with any of the investigated variables. In contrast to MMP9, total MMP2 levels correlated significantly with active MMP2 levels. In summary, total and active plasma gelatinase levels failed to identify high risk for axillary lymph node metastasis. Active plasma MMP2 was significantly increased in patients with Her2/neu overexpressing tumours, suggesting a role for Her2/neu in the signalling pathways of MMP2 activation in carcinogenesis. However, this increase was too small to be of clinical use. Furthermore, no relationship was found between plasma gelatinase levels, total or active, and any of the clinicopathological prognostic factors.

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Abbreviations

AP-2:

transcription factor activator protein

APMA:

p-aminophenylmercuric acetate

CEA:

carcinoembryonic antigen

CA15-3:

cancer antigen 15-3

DAB:

3,3-diaminobenzidine

ER:

oestrogen receptor

FISH:

fluorescence in situ hybridization

Her2/neu:

human epidermal growth factor receptor 2

MMP:

matrix metalloproteinase

MT-MMPs:

membrane type matrix metalloproteinase

PgR:

progesteron receptor

sELISA:

sandwich enzyme-linked immunoassay

TIMPs:

tissue inhibitor matrix metalloproteinase

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Authors and Affiliations

  1. Laboratory for Experimental Oncology (LEO), Department of General Medical Oncology, University Hospital Gasthuisberg, Leuven, Belgium

    J. Decock, W. Hendrickx, H. Wildiers & R. Paridaens

  2. Multidisciplinary Breast Center (MBC), University Hospital Gasthuisberg, Leuven, Belgium

    H. Wildiers, M. R. Christiaens, P. Neven, M. Drijkoningen & R. Paridaens

  3. Pathology Department, University Hospital Sint Rafaël, Leuven, Belgium

    M. Drijkoningen

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  1. J. Decock
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  2. W. Hendrickx
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  3. H. Wildiers
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  4. M. R. Christiaens
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  5. P. Neven
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  6. M. Drijkoningen
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  7. R. Paridaens
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Correspondence to R. Paridaens.

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Decock, J., Hendrickx, W., Wildiers, H. et al. Plasma Gelatinase Levels in Patients with Primary Breast Cancer in Relation to Axillary Lymph Node Status, Her2/neu Expression and other Clinicopathological Variables. Clin Exp Metastasis 22, 495–502 (2005). https://doi.org/10.1007/s10585-005-3992-2

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  • DOI: https://doi.org/10.1007/s10585-005-3992-2

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