Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in endometrial carcinoma.
BACKGROUND
Solid tumors, including endometrial carcinomas, must induce a vascular stroma to grow beyond a minimal size. The mechanisms responsible for angiogenesis in endometrial carcinoma, however, are not well defined. Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a multifunctional cytokine that is an important regulator of tumor angiogenesis. We evaluated VPF/VEGF mRNA and protein expression, as well as VPF/VEGF receptor mRNA expression, in endometrial carcinoma.


METHODS
Fourteen examples of endometrial carcinoma were evaluated by in situ hybridization; in 7 cases, benign atrophic endometrium from the same patient was also examined. Histologic sections were subjected to in situ hybridization using 35S-labeled riboprobes specific for VPF/VEGF and, in a subset of cases, riboprobes specific for the VPF/VEGF receptors flt-1 and KDR. In addition, ten examples of endometrial carcinoma were evaluated for VPE/VEGF protein expression by immunohistochemistry.


RESULTS
All 14 examples of endometrial carcinoma studied by in situ hybridization exhibited focal strong VPF/VEGF mRNA expression by tumor cells. In addition, the endothelial cells of surrounding microvessels strongly expressed flt-1 and KDR mRNAs in all ten cases examined. In contrast, no strong expression of VPF/VEGF, flt-1, or KDR mRNA was observed in the seven examples of benign atrophic endometrium studied. All ten cases of endometrial carcinoma studied by immunohistochemistry exhibited strong VPF/VEGF protein expression by tumor cells.


CONCLUSIONS
These observations suggest that VPF/VEGF is an important angiogenic factor in endometrial carcinoma.
Guidi
A J
AJ
Department of Pathology, Beth Israel Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Abu-Jawdeh
G
G
Tognazzi
K
K
Dvorak
H F
HF
Brown
L F
LF
D018269:Carcinoma, Endometrioid / Q000098:blood supply / Q000378:metabolism*; D018283:Cystadenocarcinoma, Papillary / Q000098:blood supply / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000098:blood supply / Q000378:metabolism*; D004717:Endometrium / Q000737:chemistry; D016228:Endothelial Growth Factors / Q000032:analysis* / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008222:Lymphokines / Q000032:analysis* / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis* / Q000235:genetics; D017978:Receptors, Growth Factor / Q000032:analysis* / Q000235:genetics; D040262:Receptors, Vascular Endothelial Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor