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


CONCLUSIONS
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.
Drescher
Daniel
D
Department of General and Abdominal Surgery, Johannes Gutenberg University of Mainz, Mainz, Germany.
Moehler
Markus
M
Gockel
Ines
I
Frerichs
Kirsten
K
Müller
Annett
A
Dünschede
Friedrich
F
Borschitz
Thomas
T
Biesterfeld
Stefan
S
Holtmann
Martin
M
Wehler
Thomas
T
Teufel
Andreas
A
Herzer
Kerstin
K
Fischer
Thomas
T
Berger
Martin R
MR
Junginger
Theodor
T
Galle
Peter R
PR
Schimanski
Carl C
CC
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015195:Drug Design; D004359:Drug Therapy, Combination; D005753:Gastric Mucosa / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis* / Q000037:antagonists & inhibitors*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D020794:Receptor Protein-Tyrosine Kinases