Expression of endoglin (CD105) in cervical cancer.
In this study, we have investigated the role of endoglin (CD105), a regulator of transforming growth factor (TGF)-beta(1) signalling on endothelial cells, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor-A (VEGF-A) in cervical cancer. We have measured the number and determined the location of both newly formed (CD105-positive) and the overall number of (CD31-positive) blood vessels, and bFGF and VEGF-A expression using immunohistochemistry in 30 cervical carcinoma specimens. Vascular endothelial growth factor-A mRNA expression was determined using RNA-in situ hybridisation. CD105- and CD31-positive vessels and bFGF- and VEGF-A-positive cells were predominantly present in the stroma. The presence of CD105- and CD31-positive vessels in the stroma did neither correlate with the number of VEGF-A-positive cells nor the number of bFGF-positive cells. However, the number of CD105- and CD31-positive vessels was associated with the expression of VEGF-A mRNA in the epithelial cell clusters (P=0.013 and P=0.005, respectively). The presence of CD105-positive and CD31-positive vessels was associated with the expression of alphavbeta6 (a TGF-beta(1) activator; P=0.013 and P=0.006, respectively). Clinically, the number of CD105-positive vessels associated with the number of lymph node metastasis (P<0.001). Furthermore, the presence of CD105-positive vessels within the epithelial cell clusters associated with poor disease-free survival (P=0.007).
Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
H J
HJ
Zijlmans
G J
GJ
Fleuren
S
S
Hazelbag
C F
CF
Sier
E J
EJ
Dreef
G G
GG
Kenter
A
A
Gorter
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism; D002277:Carcinoma / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D018572:Disease-Free Survival; D000071063:Endoglin; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D005353:Fibronectins; D017395:Plasminogen Activator Inhibitor 1; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011956:Receptors, Cell Surface; C051321:SERPINE1 protein, human; D053773:Transforming Growth Factor beta1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2