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

Neoplasia: An International Journal for Oncology Research. 2008;10(6):563-572 DOI 10.1593/neo.08208

 

Journal Homepage

Journal Title: Neoplasia: An International Journal for Oncology Research

ISSN: 1522-8002 (Print); 1476-5586 (Online)

Publisher: Elsevier

LCC Subject Category: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens

Country of publisher: United States

Language of fulltext: English

Full-text formats available: PDF, HTML

 

AUTHORS

Ping Gu (Department of Medicine II, Klinikum rechts der Isar, Technical University Munich Germany)
Xiangbin Xing (Department of Medicine II, Klinikum rechts der Isar, Technical University Munich Germany)
Marc Tänzer (Department of Medicine II, Klinikum rechts der Isar, Technical University Munich Germany)
Christoph Röcken (Institute of Pathology, Charité, University Hospital Berlin Germany)
Wilko Weichert (Institute of Pathology, Charité, University Hospital Berlin Germany)
Audrius Ivanauskas (Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-GuerickeUniversity Magdeburg Germany)
Matthias Pross (Department of General and Visceral Surgery, Otto-von-Guericke-University Magdeburg Germany)
Ulrich Peitz (Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-GuerickeUniversity Magdeburg Germany)
Peter Malfertheiner (Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-GuerickeUniversity Magdeburg Germany)
Roland M. Schmid (Department of Medicine II, Klinikum rechts der Isar, Technical University Munich Germany)
Matthias P.A. Ebert (Department of Medicine II, Klinikum rechts der Isar, Technical University Munich Germany)

EDITORIAL INFORMATION

Blind peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 12 weeks

 

Abstract | Full Text

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.