COMPARATIVE ANALYSIS AND CLINICAL VALUE OF THE EXPRESSION OF METALLOPROTEASES AND THEIR INHIBITORS BY INTRATUMOR STROMAL MONONUCLEAR INFLAMMATORY CELLS AND THOSE AT THE INVASIVE FRONT OF BREAST CARCINOMAS

Aims: Matrix metalloproteases (MMPs) and their inhibitors (TIMPs) play an essential role in the degradation of stromal connective tissue and basement membrane components. The dynamic analysis of these components might help predict tumor agressiveness. Methods and Results: An immunohistochemical study was performed using tissue arrays and specific antibodies against MMPs -1, 2, 7, 9, 11, 13, 14, and TIMPs -1, 2 and 3. More than 5,000 determinations on cancer specimens from 124 patients with invasive breast cancer were performed on the tumor center core as well as on the invasive front. Immunostaining for MMPs/TIMPs on mononuclear inflammatory cells (MICs) was evaluated. To identify specific groups of tumors with distinct expression profiles, data obtained from both MICs populations were analyzed by unsupervised hierarchical cluster analysis. When compared with MICs at the invasive front, intratumor MICs more frequently showed expression of MMP-7 and 14, and TIMP-3, but less frequently of MMP-9 and 11, and TIMP-2. Conclusions: Our data led us to consider the need of further studies in order to identify subsets of MICs and other protein elements of the microenviroment as attractive targets for new therapeutic strategies against cancer.