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.
Department of General and Abdominal Surgery, Johannes Gutenberg University of Mainz, Mainz, Germany.
Daniel
D
Drescher
Markus
M
Moehler
Ines
I
Gockel
Kirsten
K
Frerichs
Annett
A
Müller
Friedrich
F
Dünschede
Thomas
T
Borschitz
Stefan
S
Biesterfeld
Martin
M
Holtmann
Thomas
T
Wehler
Andreas
A
Teufel
Kerstin
K
Herzer
Thomas
T
Fischer
Martin R
MR
Berger
Theodor
T
Junginger
Peter R
PR
Galle
Carl C
CC
Schimanski
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