Decreased IL-1 RA concentration in ascites is associated with a significant improvement in overall survival in ovarian cancer

Abstract

Background: Cytokines play a major role in promoting the growth and metastatic spread of cancer cells. Interleukin-1 α and β (IL-1) and IL-1 RA are known to be critically involved in carcinogenesis and in various solid tumors. There are limited data on expression of IL-1 α, β and RA in serum and ascites in patients with advanced ovarian cancer. Objectives of this study were to investigate the level of IL-1 α, IL-1 β and IL-1 RA in serum and ascites from patients with ovarian cancer and their impact on the prognosis. Methods: Fifty-three women with ovarian cancer (OC) (33 patients with primary OC and 20 with relapsed OC) and 50 women with benign gynaecological diseases as a control group (CG) were enrolled onto this prospective study. IL-1 α, β and RA levels were analyzed in serum and ascites by ELISA technique. Results: The median age was 55 years (range 19–80) in the ovarian cancer group and 40 years (range 15–89) in the controls. The distribution of histological type of ovarian cancer was as follows: serous-papillary 43 (81.1%), 4 (7.5%) mucinous, 3 (5.7%) endometroid and 3 (5.7%) clear cell carcinoma. The concentrations of IL-1 β and RA in ascites or peritoneal fluid were significantly increased in patients with OC in comparison to the CG, for both cytokines ( p < 0.0001); also the concentration of IL-1 RA in serum was increased in OC ( p = 0.003) vs. CG. An increased level of IL-1 β in ascites correlated significantly with a poorer histopathological grading ( p = 0.038). IL-1 RA concentration in ascites was correlated with advanced FIGO stage ( p = 0.049) and the IL-1 RA serum level with ascites volume (⩽500 ml vs. >500 ml) ( p = 0.046). Patients with IL-1 RA level in ascites lower than the cut off value of 695.6 pg/ml showed a significant better progression-free median survival (24.6 vs. 12.8 months, p = 0.008) and postoperative median overall survival (34.6 vs. 17 months, p = 0.01) in comparison to patients with an IL-1 RA level in ascites higher than the cut off level. Additionally, a higher expression of IL-1 β in serum ( p = 0.004) and ascites ( p = 0.05) reduced significantly the progression-free survival. In the multivariate analysis, expression of IL-1 RA in ascites was an independent prognostic factor for good progression-free and postoperative overall survival (HR, 0.39 95% CI, 0.18–0.83, p = 0.01, HR, 0.36 95% CI, 0.16–0.8, p = 0.01). Conclusions: IL-1 RA levels in ascites lower than the cut off value of 695.6 pg/ml are associated with a significant improvement in postoperative and progression-free survival. IL-1 RA shows a prognostic relevance in ovarian cancer.