Telomerase activity in proximal and distal gastric neoplastic and preneoplastic lesions using immunohistochemical detection of hTERT

Background. The incidence of distal (corpus and antrum) gastric adenocarcinoma is decreasing with a simultaneous increase in incidence of proximal (cardia) adenocarcinoma. Epidemiological studies suggest that they may represent different diseases but corroborative molecular data are scarce. Intestinal metaplasia may have a lower malignant potential in the proximal stomach but regardless of the locations, its specificity as a predictor of carcinoma is low. Aims. The aim of this study was to establish whether human telomerase reverse transcriptase expression differs at various points in proximal versus distal gastric carcinogenesis and to test the utility of human telomerase reverse transcriptase expression as a marker of cancer risk in intestinal metaplasia. Material and methods. Wax-embedded tissue from proximal and distal stomach including normal mucosa (n = 86), intestinal metaplasia (n = 83) and carcinoma (n = 101) were used and slides were immunostained for human telomerase reverse transcriptase and pRb and scored semi-quantitatively. Results. The results showed that in both proximal and distal stomach, human telomerase reverse transcriptase expression rates increased from normal mucosa to cancer. High rates of human telomerase reverse transcriptase expression were seen in the proliferative zones of glands in intestinal metaplasia. In both the locations, loss of pRb expression correlated with higher human telomerase reverse transcriptase expression. Conclusions. In conclusion, telomerase activity appears to be an early event in both proximal and distal gastric carcinogenesis and human telomerase reverse transcriptase is expressed in intestinal metaplasia. Telomerase re-expression may be facilitated by pRb inactivation. (c) 2005 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.