Clinicopathological Significance of Human Macrophage Metalloelastase Expression in Esophageal Squamous Cell Carcinoma

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Abstract
Objective: Human macrophage metalloelastase is referred to as matrix metalloproteinase (MMP-12), its function in tumors is contradictory. The current study was undertaken to investigate the role of MMP-12 in esophageal squamous cell carcinoma (SCC). Patients and Methods: We analyzed the levels of MMP-12 mRNA expression in 67 patients with primary esophageal SCC by Northern blot analysis and the tissues were subjected to in situ hybridization analysis for MMP-12. Immunohistochemical staining was performed to detect the macrophages infiltrated in esophageal SCCs. Results: MMP-12 mRNA was detected in 27 of 67 esophageal SCC samples by Northern blot analysis. In situ hybridization and immunohistochemical staining revealed that MMP-12 mRNA signals are located mainly in tumor cells. The frequency of lymph node metastasis was significantly higher in the MMP-12-positive (MMP-12(+)) subgroup than MMP-12-negative (MMP-12(–)) subgroup (p < 0.05); furthermore, invasion was significantly deeper in the MMP- 12(+) subgroup than in the MMP-12(–) subgroup (p < 0.01). MMP-12 mRNA was inversely correlated with prognosis (p < 0.05). However, Cox multivariate analysis revealed that upregulation of MMP-12 was not related to prognosis. Conclusions: MMP-12 gene expression was associated with the progression of esophageal SCC; however, it was not an independent prognostic factor.