Abstract

Tumor invasion and metastasis are the major causes of treatment failure or death for carcinoma patients. Matrix metalloproteinases (MMPs) are zinc dependent endopeptidases implicated in tumor invasion and metastasis. The expression of MMP-2 has been previously linked to invasiveness of carcinoma cells. The MMP-2 immunoreactive protein was studied here in squamous cell carcinoma of the utrine cervix and in adenocarcinoma of the breast by using a specific monoclonal antibody in immunohistochemical stainings. Immunoreactive protein of latent MMP-2 was found to be an early event in neoplastic transformation of the cervix in 60 patients. All cases of early stage cervical carcinoma expressed the latent MMP-2 protein, suggesting that MMP-2 could be a prerequisite for invasive behavior. In early stage cervical carcinoma the high score of MMP-2 expression seemed to be associated with poor histological differentiation and lymph node metastases. The intensitivity (score) of the immunoreaction was not, however, associated with clinical behavior of this disease.

New predictive markers would be useful in selecting breast carcinoma patients to different modalities of adjuvant therapy. The MMP-2 protein has been found in breast carcinoma tumor cells in immunohistochemical analyses. MMP-2 has been found to be expressed in breast carcinoma in some preliminary studies, but there are no reports so far that would show a correlation of MMP-2 to survival in breast carcinoma. In the current study comprising 373 patients the expression of MMP-2 protein was found immunohistochemically in primary breast carcinomas. It is shown here for the first time that immunoreactive protein of MMP-2 in primary breast carcinoma is associated with a shortened relapse-free survival (RFS) or relative overall survival (OS). MMP-2 correlated to the risk of failure during the anti-estrogen adjuvant therapy in postmenopausal breast carcinoma patients with axillary lymph node metastasis without a high tumor burden. It was also found here that premenopausal patients with a node positive breast carcinoma showing MMP-2 positivity relapsed early after the primary operation. Young patients (< 40 years) with MMP-2 positive tumors had a poor outcome when compared to other node-positive premenopausal breast carcinoma patients. A patient group with a high risk for an early relapse was identified from node-positive, premenopausal breast carcinoma patients.

In conclusion, the present data show for the first time MMP-2 immunoreactive protein to be a prognostic factor in breast carcinoma, indicating further studies to explore the value of this enzyme in clinical decision making.