TY - JOUR
T1 - Frequent loss of TIMP-3 expression in progression of esophageal and gastric adenocarcinomas
AU - Gu, Ping
AU - Xing, Xiangbin
AU - Tänzer, Marc
AU - Röcken, Christoph
AU - Weichert, Wilko
AU - Ivanauskas, Audrius
AU - Pross, Matthias
AU - Peitz, Ulrich
AU - Malfertheiner, Peter
AU - Schmid, Roland M.
AU - Ebert, Matthias P.A.
N1 - Funding Information:
Address all correspondence to: Prof. Matthias P. A. Ebert, MD, Department of Medicine II, Klinikum rechts der Isar, Technical University of München, Ismaningerstr. 22, D-81675 München, Germany. E-mail: [email protected] 1This work was supported by grants from the Else Kröner-Fresenius-Stiftung (Homburg, Germany) and Astra-Zeneca (Wedel, Germany) awarded to M. Ebert, and by the Rudolf Bartling Foundation awarded to C. Röcken and M. Ebert. Received 23 January 2008; Revised 14 March 2008; Accepted 20 March 2008 Copyright © 2008 Neoplasia Press, Inc. All rights reserved 1522-8002/08/$25.00 DOI 10.1593/neo.08208
PY - 2008/6
Y1 - 2008/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=44449102334&partnerID=8YFLogxK
U2 - 10.1593/neo.08208
DO - 10.1593/neo.08208
M3 - Article
C2 - 18516293
AN - SCOPUS:44449102334
SN - 1522-8002
VL - 10
SP - 563
EP - 572
JO - Neoplasia
JF - Neoplasia
IS - 6
ER -
