Similar changes in MT concentration have been demonstrated www.selleckchem.com/products/Dasatinib.html in stomach adenocarcinoma. In a study of 35 patients with gastric adenocarcinoma where MT was quantitatively measured on resected tissues, it was found that MT was significantly lower in adenocarcinoma compared to that in normal-appearing gastric mucosa (Janssen et al, 2000). In another study on 34 patients with gastric cancer, MT immunoreactivity in the cytoplasm and surface of the tumours was absent or low in 19 cases, moderately increased in 12 patients, and greatly increased in three cases (Ebert et al, 2000). There was no association between immunoreactivity tumour stage, grade of differentiation or tumour type. This is not unexpected however, as MT is induced by a variety of inflammatory mediators as well as cytotoxic agents and irradiation.

Thus any pre-surgical radiotherapy and/or chemotherapy might affect the level of expression and localisation of MT in these studies. Our finding that MT appears quantitatively higher in the cardia and fundus than in lower regions of the stomach may reflect the glandular composition of these areas. Intense immunoreactivity has been reported in goblet cells and at the foveolar neck of gastric glands (Ebert et al, 2000). Others have demonstrated that MT is responsive to inflammatory and pre-neoplastic changes in normal tissues. In gastric cancer patients, intense immunostaining for MT was found in adjacent metaplastic and dysplastic tissues in 17 out of 34 patients (Ebert et al, 2000). Our study of 20 patients with Barrett’s epithelium clearly demonstrates that MT is increased in Barrett’s tissue above that in normal oesophagus.

The underlying reason for this increase remains unknown. There is evidence in mice that overexpression of MT in mutagen-subjected colorectal crypts arises from random stem cell somatic mutation (Jasani et al, 1998; Cook et al, 2000). Such a mechanism could account for overexpression of MT in Barrett’s oesophagus while loss of this gain mutation might occur in those lines of cells that become cancer. In the present study, there was no obvious association in MT expression between the histological markers of the presence of inflammatory cells, metaplasia or dysplasia. Indeed, two of four patients with histologically stable Barrett’s epithelium had the highest levels of MT. This may indicate that MT expression in Barrett’s mucosa is more closely related to the higher Drug_discovery MT levels found in the specialised mucosa than the pathobiology associated with cancer. Barrett’s mucosa is composed of heterogenous cell types.