Nuclear translocation of glutathione transferase omega is a progression marker in Barrett's esophagus

Abstract

Barrett's esophagus (BE) represents a major risk factor for esophageal adenocarcinoma (AC). For this reason, patients with BE are subjected to a systematic endoscopic surveillance to detect initial evolution towards non-invasive neoplasia (NiN) and cancer, that eventually occurs only in a small fraction of BE patients. This study was aimed to investigate the possible role of glutathione-S-transferaseomega 1 (GSTO1), a recently discovered member of the glutathione-S-transferase family, as a progression marker in the Barrett's disease in order to improve the diagnosis of NiN in BE and to understand the mechanisms of the progression from BE to AC. We investigated the expression and subcellular localization of GSTO1 in biopsies from patients with BE and in human cancer cell lines subjected to heath shock treatment. A selective nuclear localisation of GSTO1 was found in 16/16 biopsies with low- or highgrade NiN, while it appeared in only 4/22 BE biopsies without signs of NiN (P<0.0001). Among biopsies of BE without NiN, diffuse (nuclear and cytoplasmic) staining was found in 5/22 cases, while selective cytoplasmic localisation was found in 13/22. The 6 cases with indefinite grade of NiN were equally divided between nuclear, cytoplasmic and diffuse staining (2 each, respectively). Experiments in vitro showed that in human HeLa cancer cells, GSTO1 translocates into the nucleus as a consequence of heath shock. These findings suggested that the nuclear translocation of glutathione-S-transferase-omega 1 could be involved in the stress response of human cells playing a role in the cancer progression of Barrett's esophagus. Its immunohistochemical detection could represent a useful tool in the grading of Barrett's disease.