Differences in Stromal Immunostaining of Tumour Necrosis Factor-alpha and its Receptors in Neoplastic and Non Neoplastic Ovarian Lesions: A Cross-sectional Study

Abstract

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.