Expression of metallothionein II in intestinal metaplasia, dysplasia, and gastric cancer

Differential display is a valuable tool for the identification of different ially expressed genes in human carcinogenesis and development. The search f or differentially expressed genes in gastric cancer and its premalignant le sions may help to define molecular alterations in the gastric mucosa that m ay precede the development of gastric cancer. Using the differential displa y technique, we identified a cDNA fragment, encoding metallothionein (MT) I Ia mRNA. We performed immunohistochemical analysis using a monoclonal antib ody directed against human MT and tissues obtained from 34 patients with ga stric cancer and 20 healthy individuals to determine the expression and loc alization of MT in gastric cancer and its associated premalignant Lesions a nd to correlate our findings with histomorphological features and Helicobac ter pylori status. In addition, MT expression was assessed in gastric tissu es obtained from patients with gastric cancer and first-degree relatives of patients with gastric cancers and healthy individuals using reverse transc ription-PCR analysis. Northern blot analysis confirmed the overexpression o f MT IIa in gastric cancer. In the normal gastric tissues, no MT immunoreac tivity was observed at the superficial gastric epithelium toward the top of gastric glands. However, MT immunoreactivity was detected at the foveolar neck of the gastric glands. Immunohistochemical analysis revealed an intens e MT immunoreactivity in gastric cancer cells, independent of tumor stage, grade of differentiation, or tumor type. Furthermore, areas of dysplasia an d intestinal metaplasia also exhibited intense MT immunoreactivity, Reverse transcription-PCR analysis of gastric biopsies obtained from first-degree relatives of patients with gastric cancer revealed the frequent expression of MT Ia in this high-risk group as compared with healthy subjects (P < 0.0 1), The overexpression of MT in gastric cancer and the expression of MT in intestinal metaplasia and dysplasia, as well as the expression of MT in the gastric mucosa of first-degree relatives of patients with gastric cancer, point to a role for MT in the early process of malignant transformation of the gastric mucosa.