Comparison of the expression of tumor necrosis factor α induced protein 8 in cervical cancer and precancerous lesions of the cervix, its relationship with p16, in situ hybridization of low/high-risk human papillomavirus types, and its KI-67 cellular proliferation

Objective: Cervical cancer is the fourth most common cause of death in women throughout the world, and it maintains its importance given that cervical cancer is a significant cause of cancer-related deaths in women who live in developing countries. In today's world, Human papillomavirus (HPV) is known to be the most important risk factor for cervical cancer, and is observed in 99.7% of the patients. HPV is the most important factor in the development of cervical cancer, in the formation of premalignant lesions and their transformation to cancer. Tumor necrosis factor α induced protein 8 (TNFAIP8) is a cytosolic protein and is an antiapoptotic and oncogenic molecule which involves in immune, carcinogenesis and tumor progression processes and which could be induced with TNF-α and Nuclear factor κB which is a transcription factor. In this study, we aimed to investigate the progression of TNFAIP8, which is a newly discovered prognostic and carcinogen marker, in cervical cancer in precancerous lesions of cervix uterine, to investigate the aggressivity in cervical cancer, to compare low/high risk HPV (LR/HR HPV) with the risk of cervical cancer development, and to find out whether TNFAIP8 has a relationship with p16 expression and Ki-67 proliferation index. Materials and Methods: A total of 116 cases were included in our study consisting of 22 cervical intraepithelial neoplasia (CIN) I cases, 21 CIN II cases, 19 CIN III cases, 10 well-differentiated squamous cell carcinoma (SCC) cases, 14 moderately-differentiated SCC cases, 11 poorly-differentiated SCC cases, and 19 non-neoplastic cervix uteri cases. Immunohistochemical staining and in situ hybridization (ISH) were performed on TNFAIP8, p16 and Ki-67 to determine the low/high-risk HPV. Findings: TNFAIP8 had high staining in 48 of 116 cases, and staining rate was observed to be 41.4%. Staining rate of TNFAIP8 was observed to be 18.2% in CIN I, 14.3% in CIN II, 52.6% in CIN III, 90.0% in well-differentiated SCC, 85.7% in moderately-differentiated SCC, 81.8% in poorly-differentiated SCC, and 5.6% in non-neoplastic cervix uteri. In all cases, staining rate of p16 was 74.1%, of Ki-67 was 79.3%, of HR HPV was 85.7%, and of LR HPV was 18.9%. Conclusion: In our study, TNFAIP8 has been shown to be a prognostic marker that plays a role in carcinogenesis since more staining was observed in SCC than premalignant lesions, which may be related to the diagnosis and prognosis of the patients due to its maximum staining rate in CIN III among premalignant lesions. There was no correlation between HR HPV and LR HPV and TNFAIP8 regarding malignancy development. TNFAIP8 was also found to be not correlated with p16 and Ki-67 staining rates. Thus, it may not be a useful marker in routine like p16 and Ki-67. Keywords: Squamous cell carcinoma of the cervix uteri, precancerous lesions of the cervix uteri, TNFAIP8, p16, Ki-67, low/high-risk Human papillomavirus