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.
Highlights
Excess body weight, typically measured as high body mass index (BMI; kg/m2), is a major risk factor for endometrial cancer (EC) development [1, 2]
Our data supports both a pathogenic and prognostic role of the metabolic environment induced by obesity in endometrial cancer, and suggests that transcriptional alterations in genes regulating immune- and inflammatory responses in the tumors may be linked to the metabolic environment in which the tumor arises
This study shows that volumetric computed tomography (CT) assessment of abdominal fat compartments and waist www.impactjournals.com/oncotarget circumference provides quantitative obesity markers which are highly correlated with BMI and hepatic CT attenuation, which is a marker of steatosis (Table 2)
Summary
Typically measured as high body mass index (BMI; kg/m2), is a major risk factor for endometrial cancer (EC) development [1, 2]. Neither BMI nor other anthropometric measures including waist circumference or hip/waist ratio account for the localization of abdominal fat deposits in the subcutaneous or visceral compartments. Individuals with high quantities of visceral fat, due to increased mesenteric, omental and retroperitoneal fat storage, carry an increased risk of cardiovascular disease and type 2 diabetes [10]. They are at higher risk of developing breast-, colorectal- and esophageal cancer [11], compared to individuals with less visceral fat. Abdominal CT and MRI may allow estimation of hepatic steatosis [19], considered to be closely linked to obesity [3, 20]
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