VEGF-A and i-NOS expression are prognostic factors in serous epithelial ovarian carcinomas after complete surgical resection.
OBJECTIVE
Clinical stage at the time of diagnosis and achievement of complete macroscopic resection during initial surgery are key factors determining the outcome of ovarian cancer. However, prediction of outcome lacks accuracy and more reliable prognostic factors are required. Therefore, an analysis and evaluation of key angiogenic factors was carried out to determine their diagnostic and prognostic value in serous ovarian cancer.


METHODS
Expression levels of vascular endothelial growth factor (VEGF)-A, hypoxia-inducible factor (HIF)1-alpha and inducible nitric oxide synthase (i-NOS) were analysed by immunohistochemistry in a homogenous group of 112 patients with serous adenocarcinoma of the ovary. Vascular density as an indicator of angiogenesis was assessed using the Chalkley eyepiece method after staining for CD34. The correlation of these data with survival and established prognostic factors such as histological grade, Federation of Gynecology and Obstetrics (FIGO) stage, and residual tumour after surgery, was evaluated. Survival analyses, multivariate analyses and correlation tests were performed.


RESULTS
In the patient group with macroscopic complete tumour resection (R0) there was a significant correlation between VEGF-A and i-NOS expression. Kaplan-Meier analysis further revealed improved progression-free survival for R0 patients with VEGF-A-positive and i-NOS-negative tumours. The predictive relevance of VEGF-A regarding progression-free survival was sustained in multivariate analysis using FIGO stage, grading and resection status as fixed variables.


CONCLUSIONS
VEGF-A and i-NOS are prognostic markers for clinical outcome in serous ovarian cancer patients with macroscopic complete tumour resection (R0). Hence, pre-therapeutic assessment of VEGF-A as predictive factor for an antiangiogenic therapy might be of clinical value.
Engels
K
K
Department of Pathology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany. k.engels@em.uni-frankfurt.de
du Bois
A
A
Harter
P
P
Fisseler-Eckhoff
A
A
Kommoss
F
F
Stauber
R
R
Kaufmann
M
M
Nekljudova
V
V
Loibl
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018284:Cystadenocarcinoma, Serous / Q000098:blood supply / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D052247:Nitric Oxide Synthase Type II