Co-expression of angiogenic markers and associations with prognosis in advanced epithelial ovarian cancer: a Gynecologic Oncology Group study.
OBJECTIVE
The aim of this study was to explore the co-expression and prognostic relevance of thrombospondin-1 (THBS-1), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and VEGF receptor 1 (VEGFR-1) in epithelial ovarian cancer (EOC).


METHODS
Frozen tumor specimens with defined p53 status were obtained from 67 patients with previously untreated advanced-stage EOC who participated in a Gynecologic Oncology Group specimen-banking protocol and a phase III treatment protocol. Relative expression of the angiogenic markers was quantified by immunoblot analysis and categorized at the median angiogenic marker/actin ratio. p-values are provided as an indication of confidence in the results and to prioritize further testing.


RESULTS
An association was observed between categorized VEGF and p53 overexpression (p=0.022), and between VEGFR-1 and race (p=0.027) or histologic subtype (p=0.007). Unadjusted Cox regression analyses indicated that high compared with low THBS-1, but not VEGF or VEGFR-1, was associated with an increased risk of disease progression (hazard ratio [HR]=2.19; 95% confidence interval [CI]=1.29-3.71; p=0.004) and death (HR=1.93; 95% CI=1.12-3.32; p=0.018) whereas bFGF was associated with a reduced risk of disease progression (HR=0.60; 95% CI=0.36-0.99; p=0.046) and death (HR=0.54; 95% CI=0.32-0.93; p=0.026). After adjusting for prognostic factors including clinical characteristics and p53 overexpression, THBS-1 but not bFGF, VEGF or VEGFR-1 was associated with progression-free and overall survival.


CONCLUSIONS
These data suggest that high THBS-1 is an independent predictor of worse progression-free and overall survival in women with advanced-stage EOC. A larger prospective study is warranted for validation of these findings.
Secord
Angeles Alvarez
AA
DUMC 3079, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC 27710, USA. secor002@mc.duke.edu <secor002@mc.duke.edu>
Darcy
Kathleen M
KM
Hutson
Alan
A
Lee
Paula S
PS
Havrilesky
Laura J
LJ
Grace
Lisa A
LA
Berchuck
Andrew
A
D000368:Aged; D042501:Angiogenic Proteins / Q000096:biosynthesis*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015996:Survival Rate; D019700:Thrombospondin 1 / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis
D042501:Angiogenic Proteins; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D040281:Vascular Endothelial Growth Factor Receptor-1