Esophageal Cancer
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Feb 7, 2007; 13(5): 676-682
Published online Feb 7, 2007. doi: 10.3748/wjg.v13.i5.676
Alterations of glutathione S-transferase and matrix metalloproteinase-9 expressions are early events in esophageal carcinogenesis
Laszlo Herszenyi, Istvan Hritz, Istvan Pregun, Ferenc Sipos, Mark Juhasz, Bela Molnar, Zsolt Tulassay
Laszlo Herszenyi, Istvan Hritz, Istvan Pregun, Ferenc Sipos, Mark Juhasz, Bela Molnar, Zsolt Tulassay, 2nd Department of Medicine, Semmelweis University, Hungarian Academy of Science, Clinical Gastroenterology Research Unit, Budapest, Hungary
Author contributions: All authors contributed equally to the work.
Correspondence to: Laszlo Herszenyi, MD, PhD, 2nd De-partment of Medicine, Semmelweis University, H-1088 Budapest, Szentkiralyi u. 46, Hungary. hersz@bel2.sote.hu
Telephone: +36-1-2660816 Fax: +36-1-2660816
Received: October 7, 2006
Revised: November 13, 2006
Accepted: December 15, 2006
Published online: February 7, 2007
Abstract

AIM: To investigate the role of glutathione S-transferase (GST) and matrix metalloproteinase-9 (MMP-9) expressions in the development and progression of reflux esophagitis-Barrett’s metaplasia-dysplasia-adenocarcinoma sequence in the esophagus.

METHODS: GST and MMP-9 expressions were analyzed in 51 paraffin-embedded tissue samples by immunohistochemistry including patients with reflux esophagitis (n = 7), Barrett’s metaplasia (n = 14), Barrett and esophagitis (n = 8), Barrett and dysplasia (n = 7), esophageal adenocarcinoma (n = 8) and a control group without any histological changes (n = 7). Immunostaining was determined semiquantitatively. Statistical analysis with one-way ANOVA, LSD test and correlation analysis were performed. P value of < 0.05 was considered significant.

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, esophagitis, and Barrett and concomitant esophagitis. Barrett and concomitant 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 and concomitant dysplasia. Alterations of GST and MMP-9 were inversely correlated (r = - 0.82).

CONCLUSION: Decreased GST and increased expression 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 with dysplasia compared to non-dysplastic metaplasia indicate that these alterations may be early events in carcinogenesis. Quantification of these parameters in Barrett’s esophagus might be useful to identify patients at higher risk for progression to cancer.

Keywords: Glutathione S-transferase, Matrix metallo-proteinase-9, Barrett’s metaplasia, Esophagus, Adenocarcinoma, Dysplasia