Oncotarget

Research Papers:

High visceral fat percentage is associated with poor outcome in endometrial cancer

Karen Klepsland Mauland _, Øyvin Eng, Sigmund Ytre-Hauge, Ingvild L. Tangen, Anna Berg, Helga B. Salvesen, D8;yvind O. Salvesen, Camilla Krakstad, Jone Trovik, Erling A. Hoivik, Henrica Maria Johanna Werner, Gunnar Mellgren and Ingfrid S. Haldorsen

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Oncotarget. 2017; 8:105184-105195. https://doi.org/10.18632/oncotarget.21917

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Abstract

Karen Klepsland Mauland1,2, Øyvin Eng3, Sigmund Ytre-Hauge4,5, Ingvild L. Tangen1,2, Anna Berg1,2, Helga B. Salvesen1,2,*, Øyvind O. Salvesen6, Camilla Krakstad1,7, Jone Trovik1,2, Erling A. Hoivik1,2, Henrica Maria Johanna Werner1,2, Gunnar Mellgren3,8 and Ingfrid S. Haldorsen4,5

1Centre for Cancer Biomarkers, CCBIO, Department of Clinical Science (K2), University of Bergen, Bergen, Norway

2Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway

3Hormone Laboratory, Haukeland University Hospital, Bergen, Norway

4Department of Radiology, Haukeland University Hospital, Bergen, Norway

5Department of Clinical Medicine (K1), University of Bergen, Bergen, Norway

6Unit for Applied Clinical Research, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway

7Centre for Cancer Biomarkers, CCBIO, Department of Biomedicine, University of Bergen, Bergen, Norway

8KG Jebsen Centre for Diabetes Research, Department of Clinical Science (K2), University of Bergen, Bergen, Norway

*Deceased

Correspondence to:

Karen Klepsland Mauland, email: Karen.Mauland@uib.no

Ingfrid S. Haldorsen, email: Ingfrid.Haldorsen@uib.no

Keywords: endometrial cancer; obesity; visceral fat; hormone receptor expression; transcriptional profiling

Received: May 10, 2017    Accepted: September 03, 2017    Published: October 19, 2017

ABSTRACT

Despite evidence of increased endometrial cancer (EC) risk in obese women, the impact of obesity on clinical and histological phenotype is poorly understood. This study explored abdominal fat volumes and fat distribution quantified by computed tomography (CT), in relation to tumor characteristics and outcome. 227 EC patients with preoperative abdominal CT scans were included. Total abdominal fat volume (TAV), subcutaneous abdominal fat volume (SAV) and visceral abdominal fat volume (VAV) were quantified, and visceral fat percentage calculated (VAV%=[VAV/TAV]x100). Waist circumference (WC) and liver density (LD) were measured, and body mass index (BMI) calculated. Data for estrogen, progesterone and androgen receptor (ERα/PR/AR) expression by immunohistochemistry were available for 149 tumors, and global gene expression data for 105 tumors. High BMI, TAV, SAV, VAV and WC, and low LD, were associated with low grade endometrioid tumors and PR and AR positivity (all p≤0.03). High VAV% was associated with high age (p<0.001), aneuploidy (p=0.01) and independently predicted reduced disease-specific survival (HR 1.05, 95% CI 1.00-1.11, p=0.041). Tumors from patients with low VAV% showed enrichment of gene sets related to immune activation and inflammation. In conclusion, high VAV% independently predicts reduced EC survival. Tumors arising in patients with low VAV% show enrichment of immune and inflammation related gene sets, suggesting that the global metabolic setting may be important for tumor immune response.


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