Production of matrix metalloproteinase-2 and metalloproteinase-3 related to malignant behavior of esophageal carcinoma. A clinicopathologic study.

Abstract

Matrix metalloproteinases (MMP) are a gene family of zinc enzymes capable of degrading almost all of the extracellular matrix macromolecules in vivo. Their enzymic activities are believed to be responsible for tumor invasion and metastasis. In this study, using peroxidase-antiperoxidase method, monospecific antisera against MMP-1 (tissue collagenase), MMP-2 (type IV collagenase/72-kilodalton [KD] gelatinase), and MMP-3 (stromelysin) were applied to 29 squamous cell carcinomas and normal epithelium of the esophagus to identify cells synthesizing and secreting these enzymes. Immunoreactivity of MMP-1, -2, and -3 was observed in small cancer nests of the deeply invasive or marginal portion of the tumor. Among the 29 patients studied, the presence of at least one MMP was observed in 17 (58.6%). All three enzymes were observed in six (20.6%) patients, MMP-2 and -3 in five (17.2%) patients, only MMP-2 in three (10.3%) patients, and MMP-3 alone in three (10.3%) patients. There was a good correlation among histologic stage and tumor invasion, lymph node metastasis, and MMP expression. In particular, expression of MMP-2 and -3 was closely related to lymph node metastasis and vascular invasion. These results suggest that MMP, especially MMP-2 and -3, play an important role in tumor invasion and metastasis and that analysis of MMP-2 and -3 production is useful for evaluation of malignant potential in esophageal carcinoma.