Matrix metalloproteinase-2 immunoreactive protein: A marker of aggressiveness in breast carcinoma

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. 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. 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. 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.