Alterations of glutathione S-transferase and matrix metalloproteinase-9 expressions are early events in esophageal carcinogenesis

Abstract

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. © 2007 The WJG Press. All rights reserved.Key words: Glutathione S-transferase; Matrix metallop ro t e i n a s e -9 ; B a r re tt 's m e t a p l a s i a ; E s o p h a g u s ; Adenocarcinoma; Dysplasia INTRODUCTIONEsophageal cancer is still one of the most widespread diseases, and the early diagnosis of esophageal carcinoma correlates closely with improvement in prognosis. Barrett's esophagus (BE) is a precancerous condition of the lower esophagus in which the normal stratified squamous epithelium is replaced with specialized metaplastic columnar epithelium. Barrett's mucosa represents a type of epithelium that is completely different from the normal esophageal mucosa. BE is the main precancerous condition in the development of esophageal adenocarcinoma [1,2] . BE is diagnosed in up to 20% of patients with documented chronic gastroesophageal reflux disease (GERD). Follow-up studies have shown that BE has a 30-to 125-fold increased risk of developing into an adenocarcinoma, which emerges at a rate of approximately one cancer per 100 patient-years [3] . Barrett's adenocarcinoma displays the most rapidly increasing incidence for gastrointestinal tract cancer in the Western world. Diagnosis of Barrett's adenocarcinoma is usually made late, and consequently, is associated with poor prognosis [4][5][6] . Carcinogens are one of the inducing etiological factors for esophageal adenocarcinoma. Glutathione S-transferase (GST), a family of detoxification enzymes, plays an important role in the prevention of cancer by detoxifying numerous potentially carcinogenic compounds, ESOPHAGEAL CANCERAlterations of glutathione S-transferase and matrix metalloproteinase-9 expressions are early events in esophageal carcinogenesis www 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 si...

Barrett’s to Oesophageal Cancer Sequence: A Model of Inflammatory-Driven Upper Gastrointestinal Cancer

“…Another study found that MMP-1, -3, -7 and -10 along with TIMP-1 were increased along the sequence from BO to OAC [19]. MMP-9 demon-Picardo/Maher/O'Sullivan/Reynolds strates a similar trend [52], suggesting that alterations in these proteinases may be early events in oesophageal carcinogenesis. MMP-1, -3, -7 and -9 have been found to be prognostic biomarkers for oesophageal cancer [53].…”

Early Diagnostic Biomarkers for Esophageal Adenocarcinoma—The Current State of Play

“…Higher level of MMP-1 expression has been associated with the lymph node metastases and possibly poor patient survival (89). Expression of MMP-9 is shown to be an early event during the EAC transformation and its expression levels are correlated with the progression of the disease (90)(91)(92). Activity of MMPs is inhibited by a family of proteins called tissue inhibitors of metalloproteinases (TIMP).…”

Prognostic Significance of Matrix Metalloproteinase-9 (MMP-9) in Stage II Colorectal Carcinoma

“…It possesses proteolytic activity against type IV collagen, a major component of the BM, and has been shown to facilitate vascular smooth muscle cell migration [8]. The expression of MMP-9 is upregulated in a wide variety of human cancers [9,10]. MMP-9 expression is also significantly increased in CRC tissues [11].…”