Independent prognostic relevance of microvessel density in advanced epithelial ovarian cancer and associations between CD31, CD105, p53 status, and angiogenic marker expression: A Gynecologic Oncology Group study.
OBJECTIVE
The aims of this study were to examine prognostic significance of microvessel density (MVD) in previously-untreated, advanced epithelial ovarian cancer (EOC) and explore associations between MVD and factors that affect angiogenesis.


METHODS
MVD was determined by immunohistochemical expression of CD31 or CD105 in tumor sections from 106 women treated on GOG randomized phase III trials. Average MVD hotspots were quantified by light microscopy at high power (x400) and categorized as low (<upper quartile) or high (>or=upper quartile). Immunoblot expression of MASPIN, THBS-1, bFGF, VEGF, VEGFR-1 and p53 status (mutation and overexpression) was previously determined.


RESULTS
Of 106 evaluable cases, 25% exhibited high CD31-MVD (>24.25 vessels/high power field [HPF]) or high CD105-MVD (>19.25 vessels/HPF). After adjusting for age and stratifying by GOG performance status, stage, cell type, grade, debulking status and treatment regimen, high versus low CD105-MVD was associated with increased risk of disease progression (hazard ratio [HR]=1.873; 95% confidence interval [CI]: 1.102-3.184; p=0.020), but not death (HR=1.125; 95% CI: 0.654-1.935; p=0.670) whereas CD31-MVD was not associated with risk of disease progression (HR=1.578; 95% CI=0.918-2.711; p=0.099) or death (HR=1.678; 95% CI=0.957-2.943; p=0.071). CD31-MVD was correlated with CD105-MVD (p=0.001) and MASPIN (p=0.016). Neither CD31-MVD nor CD105-MVD was associated with p53 status, THBS-1, bFGF, VEGF or VEGFR-1.


CONCLUSIONS
High MVD assessed using CD105, a marker of proliferating endothelial cells and neoangiogenesis, but not CD31 a pan-endothelial marker, appeared to be an independent prognostic factor for worse progression-free survival in women with advanced EOC after adjusting for prognostic clinical covariates.
Rubatt
Jennifer M
JM
Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Darcy
Kathleen M
KM
Hutson
Alan
A
Bean
Sarah M
SM
Havrilesky
Laura J
LJ
Grace
Lisa A
LA
Berchuck
Andrew
A
Secord
Angeles Alvarez
AA
D000230:Adenocarcinoma / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D000071063:Endoglin; D005260:Female; D016222:Fibroblast Growth Factor 2; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis*; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D015843:Serpins; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1
D015703:Antigens, CD; D014408:Biomarkers, Tumor; C064206:ENG protein, human; D000071063:Endoglin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011956:Receptors, Cell Surface; C085344:SERPIN-B5; D015843:Serpins; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D040281:Vascular Endothelial Growth Factor Receptor-1