Background. The glutathione S-transferases (GST's) are a family of enzymes that play an important role in the prevention of cancer by detoxifying numerous potentially carcinogenic compounds. GST's conjugate reduced glutathione (GSH) to a variety of electrophilic and hydrophobic compounds, converting them into more soluble, more easily excretable compounds. The role of glutathione S-transferase P1 (GSTP1) mRNA expression in Barrett's esophagus and Barrett's associated adenocarcinoma has not been elucidated.
Materials and Methods. Using a quantitative real-time RT-PCR (Taqman,) method, we analyzed GSTP1 mRNA expression in a total of 111 specimens. The specimen were obtained from 19 patients with Barrett's esophagus (BE group), 21 patients with esophageal adenocarcinoma (EA group), and from a control group of 10 patients without evidence of Barrett's esophagus or gastroesophageal reflux disease (CG group).
Results. GSTP1 mRNA expression was detectable in all 111 samples. Analyzed according to histopathologic group, the median GSTP1 mRNA expression was highest in normal squamous esophagus epithelium, intermediate in Barrett's esophagus, and lowest in adenocarcinoma tissues (P<0.001; Kruskal-Wallis test). The median GSTP1 expression was significantly decreased in Barrett's esophagus tissues compared to matching normal squamous esophagus from either the BE group (P=0.001; Wilcoxon test) or the EA group (P=0.023). GSTPI expression levels in adenocarcinoma tissues were significantly decreased compared to both matching normal esophagus tissues from the adenocarcinoma patients (P=0.011), and compared to Barrett's esophagus tissues from the BE group (P=0.013). GSTP1 expression levels were also significantly lower in histologically normal squamous esophagus tissues from cancer patients (EA group) compared to both normal esophagus tissues from patients without cancer (BE group; P=0.007) and compared to normal esophagus tissues from the control group with no esophageal abnormality (P=0.003).
Conclusion: These results show that down-regulation of GSTP1 mRNA expression is an early event in the development of Barrett's esophagus and esophageal adenocarcinoma. Low GSTP1 expression may be a useful marker for the detection of Barrett's esophagus patients who are at high risk for progression to cancer.
