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World J Gastroenterol. Jul 14, 2007; 13(26): 3605-3609
Published online Jul 14, 2007. doi: 10.3748/wjg.v13.i26.3605
Coexpression of receptor-tyrosine-kinases in gastric adenocarcinoma-a rationale for a molecular targeting strategy?
Daniel Drescher, Markus Moehler, Ines Gockel, Kirsten Frerichs, Annett Müller, Friedrich Dünschede, Thomas Borschitz, Stefan Biesterfeld, Martin Holtmann, Thomas Wehler, Andreas Teufel, Kerstin Herzer, Thomas Fischer, Martin R Berger, Theodor Junginger, Peter R Galle, Carl C Schimanski
Daniel Drescher, Ines Gockel, Kirsten Frerichs, Friedrich Dünschede, Thomas Borschitz, Theodor Junginger, Department of General and Abdominal Surgery, Johannes Gutenberg University of Mainz, Mainz, Germany
Markus Moehler, Annett Müller, Martin Holtmann, Andreas Teufel, Kerstin Herzer, Peter R Galle, Carl C Schimanski, First Department of Internal Medicine, Johannes Gutenberg University of Mainz, Mainz, Germany
Stefan Biesterfeld, Institute of Pathology, Johannes Gutenberg University of Mainz, Mainz, Germany
Thomas Wehler, Thomas Fischer, Third Department of Internal Medicine, Johannes Gutenberg University of Mainz, Mainz, Germany
Martin R Berger, Unit of toxicology and chemotherapy, German Cancer Research Center, Germany
Author contributions: All authors contributed equally to the work.
Correspondence to: Markus Moehler, First Department of Internal Medicine, Johannes Gutenberg University of Mainz, Langenbeckstrasse 1, Mainz 55101, Germany. moehler@mail.uni-mainz.de
Telephone: +49-6131-177276 Fax: +49-6131-175595
Received: March 19, 2007
Revised: March 22, 2007
Accepted: April 16, 2007
Published online: July 14, 2007
Abstract

AIM: To define the (co-)expression pattern of target receptor-tyrosine-kinases (RTK) in human gastric adenocarcinoma.

METHODS: The (co-)expression pattern of VEGFR1-3, PDGFRα/β and EGFR1 was analyzed by RT-PCR in 51 human gastric adenocarcinomas. In addition, IHC staining was applied for confirmation of expression and analysis of RTK localisation.

RESULTS: The majority of samples revealed a VEGFR1 (98%), VEGFR2 (80%), VEGFR3 (67%), PDGFRα (82%) and PDGFRβ (82%) expression, whereas only 62% exhibited an EGFR1 expression. 78% of cancers expressed at least four out of six RTKs. While VEGFR1-3 and PDGFRα revealed a predominantly cytoplasmatic staining in tumor cells, accompanied by an additional nuclear staining for VEGFR3, EGFR1 was almost exclusively detected on the membrane of tumor cells. PDGFRβ was restricted to stromal pericytes, which also depicted a PDGFRα expression.

CONCLUSION: Our results reveal a high rate of receptor-tyrosine-kinases coexpression in gastric adenocarcinoma and might therefore encourage an application of multiple-target RTK-inhibitors within a combination therapy.

Keywords: VEGFR, EGFR, PDGFR, Cancer, Adeno-carcinoma, Gastric, Stomach