title: Serum interleukin-6 levels correlate with disease status in patients with epithelial ovarian cancer.
abstract: Interleukin-6 is a pleiotropic cytokine with a wide range of effects, including induction of B-cell and cytotoxic T-cell differentiation, and induction of acute phase reactant production by hepatocytes. Interleukin-6 also can act as an autocrine growth factor in malignancy. Various cell types produce interleukin-6, including T and B cells, monocytes, fibroblasts, and some solid tumor cells. In previous work we detected the production of substantial amounts of interleukin-6 by human ovarian cancer cells, including the ovarian cancer cell lines CAOV-3, OVCAR-3, and SKOV-3, and several primary ovarian tumor cultures. In this study we retrospectively examined 90 separate serum specimens for interleukin-6 in 36 patients with epithelial ovarian cancer. The mean serum interleukin-6 concentration of those ovarian cancer patients with macroscopic disease (n = 57) was 0.26 +/- 0.04 U/ml (mean +/- SEM). Healthy adult donors have interleukin-6 serum levels of 0.12 +/- 0.03 U/ml. Sixteen of 21 ovarian cancer patients with macroscopic disease (76%) had elevated (greater than 0.20 U/ml) levels of serum interleukin-6, with levels approaching 1 U/ml in some patients (p less than 0.01). Of those nine patients with bulky tumor (residual greater than 2 cm), eight (89%) had an elevated interleukin-6 level (mean, 0.31 +/- 0.05), while eight of 12 (66%) with minimal residual disease (less than 2 cm) had elevated levels. Only two of 15 (13%) patients who were in clinical remission and who had microscopic disease had elevated values. Of the 36 patients, 22 were CA 125 negative (less than 35 U/ml), and of these, four had elevated interleukin-6 levels. Of the 14 patients with an elevated CA 125 level, 12 (86%) had elevated interleukin-6 levels. In those 16 patients in whom serial levels of interleukin-6 were measured, rising levels were found over a 3 to 4 month interval in nine (56%); this correlated with tumor progression. Furthermore, the subsequent survival of patients was shown to correlate with the level of interleukin-6, such that patients whose levels were elevated greater than 0.20 U/ml interleukin-6 survived a mean of 12.5 months, compared with 27.2 months for patients with normal levels (p less than 0.001). These data support the concept that interleukin-6 may be a useful tumor marker in some patients with epithelial ovarian cancer, as it correlates with the tumor burden, clinical disease status, and survival.
authors.affiliation: Department of Obstetrics and Gynecology, University of California, Los Angeles School of Medicine 90024.
authors.forename: J S
authors.initials: JS
authors.lastname: Berek
authors.forename: C
authors.initials: C
authors.lastname: Chung
authors.forename: K
authors.initials: K
authors.lastname: Kaldi
authors.forename: J M
authors.initials: JM
authors.lastname: Watson
authors.forename: R M
authors.initials: RM
authors.lastname: Knox
authors.forename: O
authors.initials: O
authors.lastname: Martínez-Maza
mesh_terms: D015295:Antigens, Tumor-Associated, Carbohydrate / Q000032:analysis; D001681:Biological Assay; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D010051:Ovarian Neoplasms / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology; D011379:Prognosis; D011859:Radiography; D012016:Reference Values; D016019:Survival Analysis
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D015850:Interleukin-6