Metallothionein in human gastrointestinal cancer

Metallothionein (MT) is a small thiol-rich metalloprotein with antioxidant properties, involved in tumour pathophysiology and therapy resistance. In o rder to assess the contribution of MT in gastrointestinal carcinogenesis, t his study examined both the MT content by radioimmunoassay and the MT local ization by immunohistochemistry in pairs of neoplastic and normal-appearing human gastrointestinal tissues. In addition, the relationship between MT e xpression and major clinicopathological parameters was; assessed. The MT co ncentration of gastric carcinomas and of colorectal adenomas, carcinomas:. and liver metastases was found to be significantly lower than that of corre sponding normal-appearing tissue. A relatively high MT content, however, wa s found to be associated with the villous character of colorectal adenomas and with the Dukes' stage of colorectal carcinomas, indicating a relationsh ip between MT level and malignant potential. Immunohistochemical evaluation showed a fairly good correlation with these quantitative data. MT was foun d to be expressed at a low level and in a patchy pattern in the gastrointes tinal neoplastic and metastatic tissues, whereas in normal-appearing gastro intestinal mucosa MT was uniformly distributed in the cytoplasm and/or nucl eus of apical cells. Although in the gastric cancer patients no association was found between the MT concentration and the clinicopathological paramet ers, the strong MT expression in areas with intestinal metaplasia, known to have neoplastic potential, further points to a relationship between this a ntioxidant metalloprotein and the malignant character of cells. Gastrointes tinal neoplasms are apparently accompanied by a low level and decreased exp ression of MT, but those with a relatively high level seem to have an incre ased malignant potential. Further studies will be required to determine the clinical relevance of these observations. Copyright (C) 2000 John Wiley & Sons, Ltd.