Matrix Metalloproteinase-2 Immunoreactive Protein: a Marker of Aggressiveness in Breast Carcinoma

Background: Previous studies have shown that matrix metalloproteinase-2 (MMP-2) (a 72-kilodalton Type IV collagenase/gelatinase A) is associated with breast carcinoma, but to the authors' knowledge there are no reports showing that it is prognostic for overall survival.

Methods: Expression of the immunoreactive protein for MMP-2 was evaluated in tissue sections from primary breast carcinomas of 177 patients with a monoclonal antibody to MMP-2 using an immunohistochemical technique.

Results: Approximately 84% of the samples were MMP-2 positive, with 22% being strongly positive. Positive MMP-2 immunostaining was prognostic for shortened survival. After 10 years 56% of the patients with tumors that were strongly positive for MMP-2 were alive, whereas 88% of patients with an MMP-2 negative tumor and 70% of patients with weakly or moderately positive tumors were still alive (chi-square test = 7.4; P < 0.01, log rank analysis). MMP-2 positivity was linked with an unfavorable prognosis regardless of the age of the patient, tumor grade, receptor status of the tumor, and stage of disease. These results were confirmed by a multivariate analysis in which MMP-2 positivity emerged as an independent prognostic factor for poor survival.

Conclusions: To the authors' knowledge this study is the first time that MMP-2 immunoreactive protein has been associated strongly with a shortened survival independent of major prognostic indicators in patients with primary breast carcinoma, increasing the risk of death 3.6-fold during the first 10 years of follow-up.