ORIGINAL ARTICLES

VEGF-A and i-NOS expression are prognostic factors in serous epithelial ovarian carcinomas after complete surgical resection

K Engels¹, A du Bois², P Harter², A Fisseler-Eckhoff³, F Kommoss⁴, R Stauber⁵, M Kaufmann⁶, V Nekljudova⁷, S Loibl^6,7

¹ Department of Pathology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany
² Department of Gynaecology and Gynaecological Oncology, Dr Horst Schmidt Kliniken, Wiesbaden, Germany
³ Department of Pathology and Cytology, Dr Horst Schmidt Kliniken, Wiesbaden, Germany
⁴ Pathological Institute, Mannheim, Germany
⁵ Department of Molecular and Cellular Oncology, J Gutenberg University, Mainz, Germany
⁶ Department of Gynaecology and Obstetrics, Johann Wolfgang Goethe University, Frankfurt am Main, Germany
⁷ Department of Medicine and Research, GBG Forschungs GmbH, Neu-Isenburg, Germany

Dr Knut Engels, Johann Wolfgang Goethe University, Department of Pathology, Theodor-Stern Kai 7, 60590 Frankfurt am Main, Germany; k.engels{at}em.uni-frankfurt.de

Aims: 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- 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.

Conclusion: 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.

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