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

Cancer. 1998 Sep 15;83(6):1153-62. doi: 10.1002/(sici)1097-0142(19980915)83:6<1153::aid-cncr14>;2-4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Analysis of Variance
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Carcinoma / chemistry*
  • Carcinoma / mortality*
  • Carcinoma / pathology
  • Female
  • Gelatinases / analysis*
  • Humans
  • Immunohistochemistry
  • Matrix Metalloproteinase 2
  • Metalloendopeptidases / analysis*
  • Middle Aged
  • Neoplasm Proteins / analysis*
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Receptors, Estrogen / analysis


  • Neoplasm Proteins
  • Receptors, Estrogen
  • Gelatinases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2