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Frequent Loss of TIMP-3 Expression in Progression of Esophageal and Gastric Adenocarcinomas

By Ping Gu, Xiangbin Xing, Marc Tänzer, Christoph Röcken, Wilko Weichert, Audrius Ivanauskas, Matthias Pross, Ulrich Peitz, Peter Malfertheiner, Roland M. Schmid and Matthias P.A. Ebert


Tissue inhibitor of metalloproteinase 3 (TIMP-3) promoter methylation has been linked to loss of TIMP-3 expression in various cancers. In this study, we analyzed TIMP-3 gene methylation using MethyLight assay and TIMP-3 mRNA expression using reverse transcription–polymerase chain reaction analysis in 22 esophageal cancers, 27 gastric carcinomas, and 7 cancer cell lines. We also analyzed TIMP-3 protein expression by immunohistochemistry and its association with clinicopathological characteristics in two cohorts of gastric cancer comprising a total of 347 patients. The TIMP-3 gene was more commonly methylated in adenocarcinomas of the esophagus (9/13) and stomach (9/15) than in the corresponding nonneoplastic mucosa of the esophagus (1/8; P = .024) and stomach (2/14; P = .021). In gastric cancer patients, TIMP-3 was decreased in a diffuse-type gastric cancer and in cancers with poor differentiation and was associated with poor survival (P = .04). In summary, we observed frequent TIMP-3 promoter methylation in adenocarcinomas of the esophagus and stomach and the loss of TIMP-3 expression seems to be of clinical and prognostic relevance in these cancers

Topics: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Publisher: Elsevier
Year: 2008
DOI identifier: 10.1593/neo.08208
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