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Frequent Loss of TIMP-3 Expression in Progression of Esophageal and Gastric Adenocarcinomas1
Ist Teil von
Neoplasia (New York, N.Y.), 2008-06, Vol.10 (6), p.563-572
Ort / Verlag
Neoplasia Press Inc
Erscheinungsjahr
2008
Link zum Volltext
Quelle
Free E-Journal (出版社公開部分のみ）
Beschreibungen/Notizen
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.