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

Matthias P.A. Ebert, Thomas Günther, Juliane Hoffmann, Jun Yu, Stephan Miehlke, Hans U. Schulz, Albert Roessner, Murray Korc, Peter Malfertheiner

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Differential display is a valuable tool for the identification of differentially expressed genes in human carcinogenesis and development. The search for differentially expressed genes in gastric cancer and its premalignant lesions may help to define molecular alterations in the gastric mucosa that may precede the development of gastric cancer. Using the differential display technique, we identified a cDNA fragment, encoding metallothionein (MT) Ha mRNA. We performed immunohistochemical analysis using a monoclonal antibody directed against human MT and tissues obtained from 34 patients with gastric cancer and 20 healthy individuals to determine the expression and localization of MT in gastric cancer and its associated premalignant lesions and to correlate our findings with histomorphological features and Helicobacter pylori status. In addition, MT expression was assessed in gastric tissues obtained from patients with gastric cancer and first-degree relatives of patients with gastric cancers and healthy individuals using reverse transcription-PCR analysis. Northern blot analysis confirmed the overexpression of MT IIa in gastric cancer. In the normal gastric tissues, no MT immunoreactivity 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 intense MT immunoreactivity in gastric cancer cells, independent of tumor stage, grade of differentiation, or tumor type. Furthermore, areas of dysplasia and 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 < 0.01). 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.

Original languageEnglish (US)
Pages (from-to)1995-2001
Number of pages7
JournalCancer Research
Volume60
Issue number7
StatePublished - Apr 1 2000

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Ebert, M. P. A., Günther, T., Hoffmann, J., Yu, J., Miehlke, S., Schulz, H. U., Roessner, A., Korc, M., & Malfertheiner, P. (2000). Expression of metallothionein II in intestinal metaplasia, dysplasia, and gastric cancer. Cancer Research, 60(7), 1995-2001.