BACKGROUND: Identification of endometrial carcinoma (EC) patients at high risk of recurrence is lacking. In this study, the prognostic role of hypoxia and angiogenesis was investigated in EC patients. METHODS: Tumour slides from EC patients were stained by immunofluorescence for carbonic anhydrase IX (CAIX) as hypoxic marker and CD34 for assessment of microvessel density (MVD). CAIX expression was determined in epithelial tumour cells, with a cut-off of 1%. MVD was assessed according to the Weidner method. Correlations with disease-specific survival (DSS), disease-free survival (DFS) and distant disease-free survival (DDFS) were calculated using Kaplan-Meier curves and Cox regression analysis. RESULTS: Sixty-three (16.4%) of 385 ECs showed positive CAIX expression with high vascular density. These ECs had a reduced DSS compared to tumours with either hypoxia or high vascular density (log-rank p = 0.002). Multivariable analysis showed that hypoxic tumours with high vascular density had a reduced DSS (hazard ratio [HR] 3.71, p = 0.002), DDFS (HR 2.68, p = 0.009) and a trend for reduced DFS (HR 1.87, p = 0.054). CONCLUSIONS: This study has shown that adverse outcome in hypoxic ECs is seen in the presence of high vascular density, suggesting an important role of angiogenesis in the metastatic process of hypoxic EC. Differential adjuvant treatment might be indicated for these patients.

Biomedical Research Group in Gynecology Vall Hebron Institute of Research Universitat Autònoma de Barcelona CIBERONC Barcelona Spain

Centre for Cancer Biomarkers Department of Clinical Science University of Bergen Bergen Norway

Department of Gynaecologic Oncology Center for Gynaecologic Oncology Amsterdam The Netherlands

Department of Gynecology and Obstetrics Faculty of Medicine Masaryk University Brno Czech Republic

Department of Obstetrics and Gynaecology Canisius Wilhelmina Hospital Nijmegen The Netherlands

Department of Obstetrics and Gynaecology Radboud Institute for Health Sciences Radboud University Medical Center Nijmegen The Netherlands

Department of Obstetrics and Gynecology Haukeland University Hospital Bergen Norway

Department of Obstetrics and Gynecology Hospital del Mar PSMARB Barcelona Spain

Department of Obstetrics and Gynecology University Medical Center Freiburg Germany

Department of Oncology KU Leuven Leuven Belgium

Department of Pathology and Molecular Genetics and Research Laboratory Hospital Universitari Arnau de Vilanova University of Lleida IRBLleida CIBERONC Lleida Spain

Department of Pathology Canisius Wilhelmina Hospital Nijmegen The Netherlands

Department of Pathology Ghent University Hospital Cancer Research Institute Ghent Ghent Belgium

Department of Pathology Radboud University Medical Center Nijmegen The Netherlands

Department of Pathology University of Turku Turku Finland

Department of Radiation Oncology Radboud University Medical Center Nijmegen The Netherlands

German Cancer Consortium German Cancer Research Center Heidelberg Germany

Gynecological Department Vall Hebron University Hospital CIBERONC Barcelona Spain

Institute of Pathology Faculty of Medicine Masaryk University Brno Czech Republic

Institute of Pathology University Medical Center Freiburg Germany

Mohn Medical Imaging and Visualization Centre Department of Radiology Haukeland University Hospital Bergen Norway

Obstetrics and Gynecology Department Bichat Claude Bernard Hospital Paris France

Pathology Department Vall Hebron University Hospital CIBERONC Barcelona Spain

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