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VEGF-A and i-NOS Expression are Prognostic Factors in Serous Epithelial Ovarian Carcinomas after Complete Surgical Resection
  1. Knut Engels (k.engels{at}em.uni-frankfurt.de)
  1. Department of Pathology, Johann Wolfgang Goethe University, 60590 Frankfurt am Main, Germany
    1. Andreas du Bois (prof.dubois{at}googlemail.com)
    1. Department of Gynecology and Gynecological Oncology, Dr. Horst Schmidt-Kliniken, Wiesbaden, Germany
      1. Philipp Harter (p.harter{at}gmx.de)
      1. Department of Gynecology and Gynecological Oncology, Dr. Horst Schmidt-Kliniken, Wiesbaden, Germany
        1. Annette Fisseler-Eckhoff (annette.fisseler-eckhoff{at}hsk-wiesbaden.de)
        1. Department of Pathology and Cytology, Dr. Horst Schmidt-Kliniken, Wiesbaden, Germany
          1. Friedrich Kommoss (kommoss{at}gyn-patho.de)
          1. Pathological Institute, Mannheim, Germany
            1. Roland Stauber (stauber{at}hno.klinik.uni-mainz.de)
            1. Department of Molecular and Cellular Oncology, J Gutenberg University, Mainz, Germany
              1. Manfred Kaufmann
              1. Department of Gynecology and Obstetrics, J.W. Goethe University, Frankfurt am Main, Germany
                1. Valentina Nekljudova (valentina.nekljudova{at}germanbreastgroup.de)
                1. Department of Medicine and Research, GBG Forschungs GmbH, Neu-Isenburg, Germany
                  1. Sibylle Loibl (sibylle.loibl{at}germanbreastgroup.de)
                  1. Department of Gynecology and Obstetrics, J.W. Goethe University, Frankfurt am Main, Germany

                    Abstract

                    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 still lacks accuracy and more reliable prognostic factors are required. Therefore, we analyzed and evaluated key angiogenic factors to determine their diagnostic and prognostic value in serous ovarian cancer.

                    Methods: Expression levels of VEGF-A, HIF1-α and i-NOS were analyzed 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, 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) we found 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 even 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 anti-angiogenic therapy might be of clinical value.

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