Expression profiling and significance of VEGF-A, VEGFR2, VEGFR3 and related proteins in endometrial carcinoma.
BACKGROUND
Angiogenesis plays a key role in the progression of various tumors, including endometrial carcinomas. Several cytokines and their associated receptors are shown to be involved, particularly VEGF-A with VEGFR1, -2 and -3.


METHODS
The expressions of VEGF-A, VEGFR2 and VEGFR3 were studied in by immunohistochemistry in 76 endometrial carcinoma specimens. VEGFR2 and VEGFR3 receptor expression were also studied by qRT-PCR in 17 tumors in comparison to normal endometrium. The expression profiles were correlated with tumor type, grade, stage, lymphovascular invasion, disease free survival, and the expressions of other cytokine receptors (EGFR, CXCR1 and CXCR2).


RESULTS
Immunohistochemically, 63% of endometrial cancers expressed VEGF-A, 55% VEGFR2 and 26% VEGFR3. VEGFR3 was significantly correlated with tumor stage (p=0.02), with a trend towards poorer disease free survival (p=0.09). VEGF-A was significantly correlated with microvessel density (p<0.01). Using qRT-PCR, increased expression of VEGFR2 (17.2-fold) and VEGFR3 (21.9-fold) was seen in endometrial carcinomas compared with normal endometrium, with significant correlations among the expression levels of VEGFR2, VEGFR3, EGFR, CXCR1 and CXCR2.


CONCLUSIONS
Our study suggests that evaluation of VEGFR3 expression in tumors may provide prognostic data, and help identify patients who would best benefit from anti-angiogenic therapeutic agents. This is the first report showing correlations between the expressions levels of the different receptors.
Department of Histopathology, Imperial College London, UK. Electronic address: jayson.wang@imperial.ac.uk.
Jayson
J
Wang
Department of Gynaecology, Royal Marsden Hospital, UK. Electronic address: Alexandra.Taylor@rmh.nhs.uk.
Alexandra
A
Taylor
Department of Histopathology, Imperial College London, UK. Electronic address: raniashoweil@yahoo.com.
Rania
R
Showeil
Department of Histopathology, Imperial College London, UK. Electronic address: Pritesh.Trivedi@imperial.nhs.uk.
Pritesh
P
Trivedi
Department of Oncology, Imperial College London, UK. Electronic address: yoshiyahorimoto@hotmail.com.
Yoshiya
Y
Horimoto
Department of Histopathology, Royal Surrey County Hospital, Guildford, UK. Electronic address: izhar_dr@yahoo.com.
Izhar
I
Bagwan
Department of Histopathology, Imperial College London, UK. Electronic address: Lauren.Ewington@imperial.ac.uk.
Lauren
L
Ewington
Department of Oncology, Imperial College London, UK. Electronic address: eric.lam@imperial.ac.uk.
Eric W-F
EW
Lam
Department of Histopathology, Imperial College London, UK; Department of Pathology, Faculty of Medicine, University of Alexandria, Egypt. Electronic address: m.elbahrawy@imperial.ac.uk.
Mona A
MA
El-Bahrawy
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008024:Ligands; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics* / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000235:genetics* / Q000378:metabolism
D008024:Ligands; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C512478:EGFR protein, human; D066246:ErbB Receptors; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3
Angiogenesis; Cancer; Endometrium; Prognosis; VEGF