Introduction: Ovarian cancer has an unknown pathogenesis, and cytokines may play an important role in the aetiology and prognosis. Tumour Necrosis Factor-alpha (TNF-α) and its receptors (TNFR1 and ...TNFR2) are involved in the biology of ovarian cancer, tumour pathogenesis, and their relationship with prognostic factors. They are involved in biological processes such as immunoregulation, growth modulation, and cell differentiation. Aim: To evaluate stromal immunostaining of TNF-α and its receptors (TNFR1 and TNFR2) in malignant ovarian neoplasms, comparing it with benign ovarian neoplasms and non neoplastic ovarian lesions. Materials and Methods: A cross-sectional study was carried out at the Department of Gynaecology and Obstetrics, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil, from January 1997 to December 2020. Patients with ovarian lesions who underwent surgical treatment according to preestablished criteria (n=95) were included in the study. Patients with benign (n=37) and malignant (n=43) ovarian epithelial neoplasms, and non neoplastic ovarian lesions (n=15) were included. Data evaluated included age, parity, hormonal status (menarche or menopause), histological grade, and staging. Immunohistochemical study was performed to evaluate stromal TNF-α, TNFR1, and TNFR2. Data were analysed by GraphPad Prism 6 and IBM Statistical Package for the Social Sciences (SPSS) Statistics 20.0 software. The comparison between non neoplastic tumours, benign and malignant neoplasms was performed by the Fisher’s exact test with a significance level below 0.05. Results: Considering staining intensity 0 and 1 as “weak immunostaining” and 2 and 3 as “strong immunostaining,” TNF-α stromal immunostaining was stronger (2/3) in benign ovarian neoplasms compared to non neoplastic tumours (p-value=0.0016) and in malignant neoplasms compared to non neoplastic tumours (p-value<0.0001). TNFR1 immunostaining was stronger (2/3) in the stroma of malignant neoplasms compared to benign neoplasms (p-value<0.0001) and stronger (2/3) when comparing benign neoplasms with non neoplastic ovarian lesions (p-value=0.0002). For TNFR2, stromal immunostaining was stronger (2/3) in malignant neoplasms compared to benign neoplasms (p-value =0.0091) and stronger in malignant neoplasms compared to non neoplastic lesions (p-value=0.0004). Conclusion: A stronger immunostaining for TNF-α and its receptors was found in ovarian cancer, suggesting that they may be targets for further studies to verify their role in carcinogenesis and the progression of ovarian neoplasms. A better understanding of the role of TNF-α and its receptors in the tumour stroma of ovarian tumours may lead to future studies that may clarify the mechanisms of carcinogenesis and tumour progression.
The aim of the study was to correlate serum levels of IL-2, IL-5, IL-6, IL-8, IL-10, and TNF-α with clinical, laboratory, and pathological prognostic factors in patients with primary ovarian ...malignancy. Patients treated at the Pelvic Mass Ambulatory of the Discipline of Gynecology and Obstetrics/Oncology Research Institute (IPON) of the UFTM with confirmed diagnosis of malignant ovarian neoplasia (n = 26) were evaluated. Serum collection was performed preoperatively for the determination of tumor markers. The cytokines IL-2, IL-5, IL-6, IL-8, IL-10, and TNF-α were assayed by enzyme-linked immunosorbent assay (ELISA). The prognostic factors were compared using the Mann-Whitney test, with significance level lower than 0.05. When evaluating IL6, it was observed that higher serum levels were associated with overall survival less than 60 months (p = 0.0382). In the evaluation of IL8, higher serum levels were associated with neutrophil-to-lymphocyte ratio (NLR) ≥ 4 and platelet-to-lymphocyte ratio (PLR) ≥ 200 (p = 0.0198 and p = 0.0072, respectively), altered values of serum CA125 (p = 0.0457), and stage IIIC (p = 0.0486). Therefore, increased levels of IL-6 and IL-8 are associated with factors of worse prognosis in ovarian cancer. Additional studies with a larger sample of patients are needed to confirm the role of cytokines as prognostic factors, in the definition of treatment, and in the development of future target therapies.
