Human macrophage metalloelastase gene expression in colorectal carcinoma and its clinicopathologic significance

Abstract

Human macrophage metalloelastase (HME), also referred as matrix metalloproteinase 12, has been shown to convert plasminogen into angiostatin, an essential inhibitor of tumor angiogenesis. The current study was designed to investigate the association of HME mRNA expression with disease progression of in patients with colorectal carcinoma. The expression of HME mRNA was quantified by Northern blot analysis in tumorous (T) and nontumorous (N) tissues obtained from 54 patients with primary colorectal carcinoma, and the ratio of these two tissue types was defined as the HME T/N ratio. The prognostic significance of this ratio after surgery, along with its correlation with disease progression and metastatic potential, was evaluated. The tissues also were subjected to in situ hybridization analysis for HME. The microvessel count after immunohistochemical staining of factor VIII was used to assess angiogenesis. The HME T/N ratio showed an inverse correlation with the depth of the intestinal wall invasion, the lymphatic invasion, and the vascular invasion. The patients with overexpression of HME mRNA (HME T/N ratio > 1.191) significantly demonstrated better survival compared with those patients who did not show overexpression of HME mRNA. In situ hybridization identified the colorectal carcinoma cells as mainly responsible for the signal shown in Northern blot analysis. A considerable but not statistically significant lower microvessel density (MVD) was observed in the patients with HME overexpression. These findings demonstrate that the HME gene plays an important role in the inhibition of tumor progression in patients with colorectal carcinoma and that its overexpression is correlated closely with a better prognosis.