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Br J Cancer. 2019 May;120(11):1037-1044. doi: 10.1038/s41416-019-0461-2. Epub 2019 Apr 23.

Poor outcome in hypoxic endometrial carcinoma is related to vascular density.

Author information

1
Department of Obstetrics and Gynaecology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands. Casper.reijnen@radboudumc.nl.
2
Department of Obstetrics and Gynaecology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands. Casper.reijnen@radboudumc.nl.
3
Department of Obstetrics and Gynaecology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
4
Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
5
Department of Pathology, Ghent University Hospital, Cancer Research Institute Ghent (CRIG), Ghent, Belgium.
6
Department of Pathology and Molecular Genetics and Research Laboratory, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLleida, CIBERONC, Lleida, Spain.
7
Institute of Pathology, University Medical Center, Freiburg, Germany.
8
Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
9
Department of Obstetrics and Gynecology, University Medical Center, Freiburg, Germany.
10
German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany.
11
Biomedical Research Group in Gynecology, Vall Hebron Institute of Research, Universitat Autònoma de Barcelona, CIBERONC, Barcelona, Spain.
12
Gynecological Department, Vall Hebron University Hospital, CIBERONC, Barcelona, Spain.
13
Pathology Department, Vall Hebron University Hospital, CIBERONC, Barcelona, Spain.
14
Department of Obstetrics and Gynecology, Hospital del Mar, PSMARB, Barcelona, Spain.
15
Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway.
16
Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.
17
Mohn Medical Imaging and Visualization Centre, Department of Radiology, Haukeland University Hospital, Bergen, Norway.
18
Department of Pathology, University of Turku, Turku, Finland.
19
Obstetrics and Gynecology Department, Bichat-Claude Bernard Hospital, Paris, France.
20
Department of Gynecology and Obstetrics, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
21
Institute of Pathology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
22
Department of Obstetrics and Gynaecology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.
23
Department of Pathology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.
24
Department of Oncology, KU Leuven, Leuven, Belgium.
25
Department of Gynaecologic Oncology, Center for Gynaecologic Oncology, Amsterdam, The Netherlands.

Abstract

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.

PMID:
31011231
DOI:
10.1038/s41416-019-0461-2

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