Vascular permeability factor (vascular endothelial growth factor) expression and angiogenesis in cervical neoplasia.
BACKGROUND
Angiogenesis is a critical factor in the progression of solid tumors, including cervical cancers. The mechanisms responsible for angiogenesis in cervical neoplasia, however, are not well defined.


OBJECTIVE
Our goal was to determine the relationship between angiogenesis and the expression of the angiogenic cytokine vascular permeability factor (VPF), also known as vascular endothelial growth factor, and its receptors in cervical neoplasia.


METHODS
Sixty-six cervical biopsy specimens were evaluated; among these, 16 samples were designated as benign, 17 as low-grade squamous intraepithelial lesions, 18 as high-grade squamous intraepithelial lesions, and 15 as invasive squamous cell carcinomas. Histologic sections immunostained for factor VIII-related antigen were evaluated quantitatively for microvessel density and for the presence of epithelial-stromal vascular cuffing. Sections were also evaluated for VPF messenger RNA (mRNA) expression by in situ hybridization.


RESULTS
VPF mRNA expression, epithelial-stromal vascular cuffing, and microvessel density counts were significantly increased in invasive carcinoma and in high-grade intraepithelial lesions as compared with low-grade intraepithelial lesions and benign squamous epithelium. Vascular cuffing and increased microvessel density counts were also significantly associated with increased VPF mRNA expression.


CONCLUSIONS
These observations suggest that VPF is an important angiogenic factor in cervical neoplasia.
Guidi
A J
AJ
Department of Pathology, Beth Israel Hospital, Boston, MA 02215, USA.
Abu-Jawdeh
G
G
Berse
B
B
Jackman
R W
RW
Tognazzi
K
K
Dvorak
H F
HF
Brown
L F
LF
D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000737:chemistry; D002584:Cervix Uteri / Q000098:blood supply* / Q000737:chemistry*; D016228:Endothelial Growth Factors / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008222:Lymphokines / Q000032:analysis*; D009389:Neovascularization, Pathologic / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D017978:Receptors, Growth Factor / Q000032:analysis* / Q000235:genetics; D011975:Receptors, Mitogen / Q000032:analysis* / Q000235:genetics; D040262:Receptors, Vascular Endothelial Growth Factor; D002583:Uterine Cervical Neoplasms / Q000098:blood supply* / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017978:Receptors, Growth Factor; D011975:Receptors, Mitogen; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor