Comparative study of the expression of metalloproteases and their inhibitors in different localizations within primary tumours and in metastatic lymph nodes of breast cancer

P>Studies on metastasic lesions from human carcinomas are scarce. Therefore there is a need for such studies to identify the expression of the biological factors that will help in the assessment of the natural history of breast cancer. Here an immunohistochemical study was performed using tissue arrays and specific antibodies against matrix metalloproteinases (MMPs)-1, 2, 7, 9, 11, 13, 14 and tissue inhibitors of metalloproteases (TIMPs)-1, 2 and 3 in 39 patients with breast cancer. Specimens from 39 patients with node-positive carcinomas were examined and the analysis was performed at the central core of the tumour, at the invasive front, and in the metastasic axillary lymph nodes (MALNs). Global expression of MMP-1, 7 and 14, TIMP-1, and 3, were significantly higher at the centre of the tumour compared with the invasive front or the MALNs. Significantly higher expression of MMP-7 and 14, and TIMP-3, by fibroblast-like cells and mononuclear inflammatory cells (MICs) was seen in MALNs. In addition, in the tumour centre, the expression of MMP-11 and TIMP-1 and 2 by MICs, as well as TIMP-2 expression by fibroblast-like cells, were associated significantly with the occurrence of distant metastasis. In contrast, TIMP-3 expression by tumour cells or by fibroblast-like cells in this same tumour locations, as well as TIMP-1 expression by fibroblast-like cells at the invasive front, were associated significantly with poor prognosis. However, the expression of all of these biological factors in MALNs was not associated with the development of distant metastasis. Our data suggest that there is prognostic relevance to the expression of MMPs and TIMPs in the stromal cells of primary tumours, rather than to the expression of these enzymes in MALNs.