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Frequent loss of TIMP-3 expression in progression of esophageal and gastric adenocarcinomas.


ABSTRACT: 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.

SUBMITTER: Gu P 

PROVIDER: S-EPMC2386541 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

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Frequent loss of TIMP-3 expression in progression of esophageal and gastric adenocarcinomas.

Gu Ping P   Xing Xiangbin X   Tänzer Marc M   Röcken Christoph C   Weichert Wilko W   Ivanauskas Audrius A   Pross Matthias M   Peitz Ulrich U   Malfertheiner Peter P   Schmid Roland M RM   Ebert Matthias P A MP  

Neoplasia (New York, N.Y.) 20080601 6


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  ...[more]

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