The
glutathione S-
transferases (
GSTs) are a family of
enzymes that play an important role in the prevention of
cancer by detoxifying numerous potentially carcinogenic compounds.
GSTs conjugate
reduced glutathione to a variety of electrophilic and hydrophobic compounds, converting them into more soluble, more easily excretable compounds. Decreased
glutathione S-transferase-pi (GSTPI)
enzyme activity has been reported in
Barrett's esophagus, and an inverse correlation was demonstrated between GST
enzyme activity and
tumor incidence in the gastrointestinal tract, but the role of GSTPI messengerRNA (
mRNA) expression in
Barrett's esophagus and associated
adenocarcinomas is uncertain. The purpose of this study was to investigate the role of GSTPI
mRNA and
protein expression in the development and progression of the Barrett's
metaplasia-dysplasia-
adenocarcinoma sequence, and to investigate the potential of GSTPI quantitation as a
biomarker in the clinical management of this disease. GSTPI
mRNA expression levels, in relation to the housekeeping gene
beta-actin, were analyzed using a quantitative real-time reverse transcription-polymerase chain reaction method (TaqMan) in 111 specimens from 19 patients with
Barrett's esophagus without
carcinoma (BE group), 21 patients with Barrett's-associated
adenocarcinoma (EA group), and a control group of 10 patients without evidence of
Barrett's esophagus or chronic
gastroesophageal reflux disease. GSTPI
mRNA expression was detectable in all 111 samples investigated. Analyzed according to histopathologic group, the median GSTPI
mRNA expression was highest in normal squamous esophagus epithelium, intermediate in
Barrett's esophagus, and lowest in
adenocarcinoma tissues (P < 0.001). The median GSTPI expression was significantly decreased in
Barrett's esophagus tissues compared to matching normal squamous esophagus from either the BE group (P = 0.001) or the EA group (P = 0.023). GSTPI expression levels in
adenocarcinoma tissues were decreased compared to matching normal esophagus tissues from the patients with
adenocarcinoma (P = 0.011). Furthermore, GSTPI
mRNA expression values were significantly different between metaplastic, dysplastic, and
adenocarcinoma tissues (P = 0.026). GSTPI expression levels were also significantly lower in histologically normal squamous esophagus tissues from patients with
cancer (EA group) compared to both normal esophagus tissues from patients without
cancer (BE group; P = 0.007) and normal esophagus tissues from the control group with no esophageal abnormality (P = 0.002). GSTPI
protein expression was generally highest in the basal layer of normal squamous esophagus epithelium and lowest in
adenocarcinoma cells, with Barrett's cells showing intermediate staining intensity. Our results show that downregulation of GSTPI expression is an early event in the development of
Barrett's esophagus and esophageal
adenocarcinoma. Loss of GSTPI expression may have an important role in the development and progression of this disease.