Supervised Clustering of Adipokines and Hormonal Receptors Predict Prognosis in a Population of Obese Women with Type 1 Endometrial Cancer

Abstract

Obesity is a major risk factor for endometrial cancer (EC). Yet, its impact on prognosis is controversial. Obesity is associated with metabolic and hormonal dysregulation as well as adipokines increase. The aim of this study was to characterize the expression of biological factors related to obesity within the tumor and evaluate their impact on prognosis. One hundred and thirty-six patients, including 55 obese patients, with endometrioid type I EC operated by total hysterectomy were included in this retrospective study conducted in a Tertiary teaching hospital between 2000 and 2013. Immunohistochemistry (IHC) study was performed on type I EC tumor samples using five adipokines (SPARC, RBP4 (Retinol Binding Protein 4), adiponectin, TNF α, IL-6) and hormonal receptors (estrogen receptor and progesterone receptor). Supervised clustering of immunohistochemical markers was performed to identify clusters that could be associated with prognostic groups. The prognosis of the obese population was not different from the prognosis of the general population. Adipokine expression within tumors was not different in these two populations. In obese population, we found three clusters where co-expression was associated with a recurrence group in comparison with a non-recurrence group and four clusters where co-expression was associated with the high risk FIGO (International Federation of Gynecology and Obstetrics) stage I group in comparison of low risk FIGO stage I group. While obesity does not appear as a prognostic factor in endometrioid type I EC, the co-expression of biological factors in IHC on hysterectomy specimens allowed to distinguish two prognostic groups in obese population.

Adipocytokines and their relationship to endometrial cancer risk: A systematic review and meta-analysis

“…Both cytokines have been reported to be increased in endometrial cancer and their pro-inflammatory actions play a role in cancer growth and metastasis by inducing reactive oxygen species and subsequent DNA damage and DNA repair inhibition [18]. IL-6 was found to be overexpressed in the stroma of endometrial cancer cells and TNFα was associated with poor survival [19,20]. However, other studies have not reported such an increase and found no difference in the expression of IL-6 in endometrial cancer and at the various clinical stages [21].…”

Relationship of Retinol Binding Protein Four Serum Level on Endometrial Hyperplasia and Endometrial Carcinoma

“…[6][7][8][9][10] Endometrial hyperplasia is a pathological condition in the endometrium in the form of increased proliferation of the endometrial glands resulting in changes in the ratio of glands and stroma, shape and size of the gland, the glandular structure increases to 2-3 layers and has the potential to be an atypical form of cells when there is no balance of inhibitors and the initiator of the proliferation of glandular cells. [9][10][11] With the imbalance between estrogen and progesterone where there is a state of Unopposed Estrogen that will cause endometrial thickening. Estrogen hormones known to be produced in the ovaries are also produced on adipose tissue.…”

Insulin Resistance and Endometrial Cancer: Emerging Role for microRNA

“…Importantly, leptin plays a proinflammatory role, contributing to the generation and maintenance of low-grade inflammation, recently also linked to EC [42]. However, literature data regarding circulating levels of adiponectin and leptin in EC report conflicting results [111,123,124]. Increased circulating adiponectin and adiponectin/leptin ratio and decreased leptin concentration were shown to be associated with reduced risk for EC [125].…”