Citocinas e Óxido Nítrico Intracístico em Neoplasias Ovarianas

Abstract

INTRODUCTION: Ovarian cancer still represents a major challenge for oncology gynecology and most patients are diagnosed at an advanced stage. It is a heterogeneous disease and many studies indicate that chronic inflammation is one of the main mechanisms in its pathogenesis. There is a need for the development of new biomarkers for the diagnosis and prognosis of ovarian cancer, which may ideally serve as targets for new therapeutic modalities. For this, our objectives were to compare the dosage of cytokines (IL-2, IL-5, IL-6, IL-8, IL-10 and TNF-α) and nitric oxide (NO) metabolites in non-neoplastic tumors, benign neoplasms and malignant primary ovarian neoplasms; and to relate the dosage of cytokines and intracellular NO metabolites with clinical, laboratory and pathological parameters of patients with primary ovarian malignancy. PATIENTS AND METHODS: We assessed 110 patients with an adnexal mass diagnosis. The inclusion criterion was a postoperative diagnosis of a non-neoplastic ovarian tumor or ovarian neoplasm by anatomopathological paraffin. The anatomopathological evaluation of tumors and the staging of the malignant tumors were performed according to the criteria of the International Federation of Gynaecology and Obstetrics - FIGO. All ovarian tumors underwent puncture soon after excision of the cyst. The concentrations of IL-2, IL-5, IL-6, IL- 8, IL-10 and TNF-α were quantified by enzyme-linked immunosorbent assay (ELISA) and nitrate quantification determined by enzymatic reduction of nitrite by nitrate reductase. The results were analyzed by Kruskal-Wallis test, with Dunn's post-test. The evaluation of the prognostic factors was performed by Mann Whitney test. A p-value < 0.05 was considered statistically significant. RESULTS: There was higher IL-6, IL-8 and NO levels in the ovarian malignancy group when compared to the benign neoplasm group (p = 0.0006; p = 0.0110 and p = 0.0178, respectively). There was higher IL-2 levels in tumors with histological grade 1 when compared to histological grades 2 and 3 (p = 0.0112). IL-6 levels were higher in patients with anemia (p = 0.0232). IL-8 levels were higher in patients with the Neutrophil/Lymphocyte Ratio (NLR) greater than 2.6 (p = 0.0443), and in patients with disease-free survival less than 36 months (p = 0.0288). IL-10 levels were higher in patients with normal CA 19.9 (p = 0.0019). TNF-α levels were higher in tumors with Type 2 carcinogenesis model (p = 0.0364), and in patients with Platelet/Lymphocyte Ratio (PLR) less than 300 (p = 0.0420). NO levels were higher in patients with NLR less than 2.6 (p = 0.0443), as well as in patients with CA 19.9 greater than 35 U/mL (p = 0.0112).12 CONCLUSION: Higher intracystic values of some cytokines are associated with worse prognostic factors in ovarian cancer, especially IL-6 and IL-8. Further studies with a larger sample of patients are needed to confirm the role of cytokines as diagnostic and prognostic factors.