Expression of metalloproteases and their inhibitors in primary tumors and in local recurrences after mastectomy for breast cancer

Abstract

Aims: To investigate the expression of matrix metalloproteases (MMPs) and their inhibitors (TIMPs) in patients who develop local recurrence (LR) after mastectomy.

Methods: We analyzed the expressions of MMP-1, -2, -7, -9, -11, -13, -14, TIMP-1, -2, and -3, using immunohistochemical techniques, in primary tumors from patients without tumoral recurrence (n = 50), patients who developed distant metastasis (n = 50), and from patients who develop LRs (n = 25). LRs of the latter group were also analyzed for MMPs expression. All the patients underwent mastectomy.

Results: Score values for all MMPs and TIMPs were significantly higher in primary tumors of patients with distant metastasis. Primary tumors from patients with LR have lower expressions of MMPs and TIMPs compared with those from patients who developed distant metastasis, and with patients without recurrence for some MMPs. Remarkably, however, primary tumors from patients with LR showed significantly higher percentage of TIMP-1 and 2 expression in stromal cells compared to primary tumors from patients with distant metastasis or primary tumors from patients without tumoral progression. Furthermore, LRs had significantly higher MMP-9 expression than their corresponding primary tumors.

Conclusions: Our data indicate differences in MMPs/TIMPs expression between primary tumors of patients with LRs and of those with distant metastasis, both after mastectomy for breast cancer.

Fig. 1

Up Examples of tissue arrays with immunostaining for each protein evaluated. a MMP-1, b MMP-2, c MMP-7, d MMP-9, e MMP-11, f MMP-13, g MMP-14, h TIMP-1, i TIMP-2, j TIMP-3. Down (left) 400× Immunostaining for TIMP-2 in mononuclear inflammatory cells, (right) 400× Immunostaining for MMP-11 in fibroblastic cells

Fig. 2

Comparative expression of MMP-9 in primary tumors and local recurrence