Alterations of MMP-9 and glutathione S-transferase expressions in the esophagitis-Barrett's metaplasia-dysplasia-adenocarcinoma sequence of the esophagus

Background: Barrett's esophagus is the main precancerous condition for development of esophageal adenocarcinoma. Glutathione S-transferase (GST) plays a part in prevention of cancer by detoxifying numerous potentially carcinogenic compounds. Matrix metalloproteinases play an important role in extracellular matrix remodelling during the process of tumor progression. Decreased GST activity has been reported in Barrett's dysplasia and adenocarcinoma and increased levels of matrix metalloproteinase-9 (MMP-9) have been observed in esophageal squamous cell carcinoma, but their role in early stages of esophageal carcinogenesis is still uncertain.

Aim: To investigate the role of MMP-9 and GST expressions in development and progression of reflux esophagitis-metaplasia-dysplasia-adenocarcinoma sequence.

Materials and methods: MMP9 and GST expressions were analyzed in 51 paraffin-embedded tissue samples by immunohistochemistry including patients with esophagitis (n=7), Barrett's metaplasia (n=14), Barrett+esophagitis (n=8), Barrett+dysplasia (n=7), esophageal adenocarcinoma (n=8) and a control group without histological changes (n=7). Statistical analysis with one-way ANOVA was performed.

Results: GST expression was significantly higher while MMP-9 expression was significantly lower in control group compared to Barrett's metaplasia and the other groups. No major changes were observed between Barrett's metaplasia, esophagitis and Barrett+esophagitis. Barrett+dysplasia and adenocarcinoma revealed a significant lower expression of GST and higher levels of MMP-9 compared to all other groups. Adenocarcinoma showed almost no expression of GST and significantly higher levels of MMP-9 than Barrett+dysplasia. Alterations of GST and MMP-9 were inversely correlated (r=-0.82).

Conclusions: Down-regulation of GST and up-regulation of MMP-9 in Barrett's metaplasia-dysplasia-adenocarcinoma sequence as compared to normal tissue suggest their association with esophageal tumorigenesis. Loss of GST and gain of MMP-9 in Barrett's esophagus with dysplasia compared to non-dysplastic metaplasia indicate that these alterations may be early events in carcinogenesis.