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

Autor: Ping Gu, Xiangbin Xing, Marc Tänzer, Christoph Röcken, Wilko Weichert, Audrius Ivanauskas, Matthias Pross, Ulrich Peitz, Peter Malfertheiner, Roland M. Schmid, Matthias P.A. Ebert
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Zdroj: Neoplasia: An International Journal for Oncology Research, Vol 10, Iss 6, Pp 563-572 (2008)
Druh dokumentu: article
ISSN: 1476-5586
1522-8002
DOI: 10.1593/neo.08208
Popis: 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.
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