Coexpression of receptor-tyrosine-kinases in gastric adenocarcinoma--a rationale for a molecular targeting strategy?

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, PDGFR alpha/beta 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%), PDGFR alpha (82%) and PDGFR beta (82%) expression, whereas only 62% exhibited an EGFR1 expression. 78% of cancers expressed at least four out of six RTKs. While VEGFR1-3 and PDGFR alpha 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. PDGFR beta was restricted to stromal pericytes, which also depicted a PDGFR alpha 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.

• Authors: 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
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 13 Issue 26 Pg. 3605-9 (Jul 14 2007) ISSN: 1007-9327 [Print] United States
• PMID: 17659711 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Protein Kinase Inhibitors
• Receptor Protein-Tyrosine Kinases

Topics

• Adenocarcinoma (drug therapy, enzymology, pathology)
• Antineoplastic Agents (pharmacology, therapeutic use)
• Drug Design
• Drug Therapy, Combination
• Gastric Mucosa (enzymology)
• Humans
• Immunohistochemistry
• Protein Kinase Inhibitors (pharmacology, therapeutic use)
• Receptor Protein-Tyrosine Kinases (analysis, antagonists & inhibitors)
• Reverse Transcriptase Polymerase Chain Reaction
• Stomach Neoplasms (drug therapy, enzymology, pathology)