Overexpression of MMP21 and MMP28 is associated with gastric cancer progression and poor prognosis

Abstract

Matrix metalloproteinase (MMP)-21 and MMP-28, or epilysin, are overexpressed during the invasion and metastasis of solid tumors. The present study investigated MMP-21 and MMP-28 expression levels in human gastric cancer using tissue microarray (TMA) analysis, and determined their association with clinicopathological characteristics and patient prognosis. TMA blocks, including 436 cases of gastric cancer and 92 non-cancerous adjacent gastric tissues, were investigated using immunohistochemistry. Staining results were analyzed statistically in association with various clinicopathological characteristics and overall survival. The MMP-21 and MMP-28 positive detection rate was 31.9% (139/436) and 34.4% (150/436), respectively, in the gastric carcinoma tissue specimens. MMP-21 and MMP-28 expression levels were negative in the 92 normal gastric tissue samples. In patients with gastric cancer, positive expression of MMP-21 and MMP-28 was correlated with tumor diameter, depth of invasion, vessel invasion, lymph node and distant metastases and tumor-node-metastasis stage. The overall survival rate was significantly lower in MMP-21 and MMP-28-positive compared with negative patients. Cox multivariate analysis revealed that MMP-21 and MMP-28 levels were independent predictors of survival in patients with gastric cancer. These findings emphasize the importance of MMP-21 and MMP-28, which may serve as novel and independent prognostic markers for the invasion and metastasis of human gastric cancer.