Proinflammatory and immunosuppressive serum, ascites and cyst fluid cytokines in patients with early and advanced ovarian cancer and benign ovarian tumors

Abstract

Objective: To analyze the profiles of interleukin-2 (IL-2), IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1) and interferon-gamma (IFN-gamma) in serum and the tumor microenvironment (cyst fluid, ascites) in women with ovarian cancer or benign ovarian tumors to find the differences in their immunological status. We also estimated serum cytokines as biomarkers to distinguish preoperatively between malignant or benign character of tumors.

Design: Prospective study.

Setting: Tertiary referral hospital.

Population: 51 women with epithelial ovarian cancer, 26 with benign ovarian tumors of epithelial origin and 21 healthy controls.

Methods: The levels of cytokines were measured using ELISA sets.

Results: We did not found differences in the levels of IFN-gamma, TNF-alpha and IL-2 in all fluids isolated from patients with malignant or benign tumors. Women with advanced cancer had significantly higher serum IL-6, IL-10 and TGF-beta1 levels than women with early stages or benign tumors. Moreover, women with very advanced cancer in whom the optimal cytoreduction was disabled had the highest serum levels of IL-10, TGF-beta1 and IL-8. The concentrations of IL-6 and IL-8 were higher in ascites of cancer patients than in ascites of women with benign tumors. The areas under curves constructed for the selected cutoff serum cytokines levels (AUC-ROC) showed good predictive values for IL-6 (0.87), IL-10 (0.836) and IL-8 (0.797).

Conclusions: Our results indicate on intensified inflammatory process in women with ovarian cancer (accompanied by their immunosuppression). Preoperative analysis of serum IL-6, IL-10 and IL-8 may improve the differential diagnosis of ovarian tumors.