ABSTRACT
The development of new biomarkers for the diagnosis and prognosis of ovarian cancer may provide an opportunity for new therapies. In this study, we aimed to compare cytokines (interleukin [IL]-2, IL-5, IL-6, IL-8, IL-10 and tumour necrosis factor [TNF]-α) and nitric oxide (NO) metabolite levels in non-neoplastic tumours, benign primary ovarian tumours and malignant primary ovarian neoplasms. The secondary aim was to relate cytokine and intracystic NO metabolite levels to clinical, laboratory and pathologic characteristics for patients with primary ovarian malignancies. We evaluated 110 patients with adnexal masses. Cytokine concentrations were quantified by enzyme-linked immunosorbent assay and nitrate concentrations by enzymatic reduction of nitrite by nitrate reductase. Patients with malignant neoplasms had higher IL-6, IL-8 and NO levels compared to patients with benign neoplasms. Histologic grade 1 tumours were associated with elevated IL-2 levels, whereas anaemia was associated with elevated IL-6 levels. On average, those patients with elevated IL-8 levels also had a neutrophil/lymphocyte ratio (NLR) greater than 2.6 and less than 36 months of disease-free survival (DFS). Patients with normal CA 19-9 levels had elevated IL-10 levels. TNF-α was elevated in patients with two carcinogenesis and those with a platelet/lymphocyte ratio (PLR) less than 300. NO levels were higher in patients with an NLR less than 2.6 and CA 19-9 greater than 35 U/ml. Elevated intracystic cytokine levels, especially IL-6 and IL-8, are associated with worse prognosis in ovarian cancer.
Subject(s)
Biomarkers, Tumor/metabolism , Interleukin-6/metabolism , Interleukin-8/metabolism , Nitric Oxide/metabolism , Ovarian Cysts/immunology , Ovarian Neoplasms/immunology , Ovary/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Carcinogenesis , Child , Female , Humans , Middle Aged , Ovarian Cysts/diagnosis , Ovarian Cysts/mortality , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/mortality , Ovary/pathology , Survival Analysis , Young AdultABSTRACT
Neutrophil migration is a key event in the inflammatory response of any origin, and neutrophils may present antitumor activity. We investigated the number and function of circulating neutrophils obtained from patients with cervical neoplasia at different stages. Patients with preinvasive (cervical intraepithelial neoplasia, CIN3, n= 6) or microinvasive ([MICRO] stage IA1, n= 4) neoplasia were evaluated together as CIN/MICRO group (n= 10), while patients at stages II-IV were evaluated as invasive group (INV, n= 12). Healthy women served as controls (n= 15). For patients, analysis of leukogram on diagnosis showed a significant elevated neutrophil count in INV group compared with that in CIN/MICRO group. A neutrophil/lymphocyte ratio >/=5 was observed in 67% patients from INV group compared with only 10% from CIN/MICRO group. Neutrophil migration, assayed in a microchemotaxis chamber in response to the chemoattractants (10(-7) M) N-formyl-l-methionyl-l-leucyl-l-phenylalanine, leukotriene B(4), or interleukin-8, was reduced in INV group than in controls or CIN/MICRO group. Surgical treatment in randomly selected patients from CIN/MICRO group (four CIN, one MICRO) increased neutrophil migration to all chemoattractants compared with time on diagnosis. The serum levels of nitric oxide (NO) metabolites, assayed by the Griess reaction, were higher in patients (n= 19) than in controls (n= 15), without differences related to tumor stage, but were reduced in patients after surgery compared with pretreatment (n= 10). Taken together, the results suggest that neutrophils play a role in the host response in cervical cancer. Soluble circulating mediators released by tumor cells, such as NO, could interfere early in the capacity of neutrophils to migrate, thus impairing host immune response.
