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    Nicotinamide N-Methyltransferase expression in cervical adenocarcinoma and its clinical significance
    (SPRINGER INDIA, 2019) Akar, Serra.; Harmankaya, İsmail.; Uğraş, Serdar.; Çintesun, Ersin.; Çelik, Çetin.
    IntroductionNicotinamide N-methyltransferase (NNMT) is a metabolic enzyme increasingly implicated in tumor progression and resistance to treatment. It is overexpressed in human cancers including glioblastoma, gastric, pancreatic, lung and colorectal cancers. The role of NNMT in cervical adenocarcinoma has not been studied thus far. We aimed to evaluate expression of NNMT in cervical adenocarcinoma and investigate its prognostic significance.MethodsNNMT expression was assayed in 18 cases of cervical adenocarcinoma and 19 cases of benign cervical tissue. NNMT immunoreactivity was scored by multiplying staining intensity with percentage of immunoreactive cells.ResultsThe expression of NNMT was significantly higher in cervical adenocarcinoma than in benign tissue (p=0.024). NNMT expression was significantly higher in patients with locally advanced than early cervical cancer (p=0.031). NNMT expression was higher in patients with tumor size greater than 4cm and in those with poorly differentiated tumors compared to patients with tumors of 4cm or less and well-moderate differentiation, respectively (p=0.044, p=0.014).ConclusionAlthough on a preliminary level, this is the first study to detect an overexpression of NNMT in cervical adenocarcinoma and an increased expression associated with advanced stage, increased tumor size and poor differentiation. NNMT has been shown to carry prognostic and therapeutic importance in a variety of cancers, and it can be a potential treatment target in cervical adenocarcinomas.
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    Nicotinamide N-Methyltransferase expression in high-grade serous carcinoma and its association with survival
    (SPRINGER INDIA, 2019) Akar, Serra.; Harmankaya, İsmail.; Uğraş, Serdar.; Çelik, Çetin.
    Introduction Ovarian cancer is the most lethal gynecological malignancy. Mechanisms involved in the progression of primary high-grade serous carcinoma (HGSC) into metastatic carcinoma are not understood. Nicotinamide N-methyltransferase (NNMT) is overexpressed in cancer, and its overexpression leads to epigenetic changes through hypomethylation of histones. It plays a role in epithelial-mesenchymal transition and sustenance of cancer stem cells. NNMT expression in primary and metastases of ovarian carcinoma and its relationship with survival have not been studied before. Materials and Methods We compared the expression of NNMT between primary and matched synchronous metastatic carcinoma of patients, diagnosed with HGSC. Benign ovarian and omental tissues were used as controls. The relationships between NNMT expression and relapse-free and disease-specific survival were analyzed. Results NNMT expression in metastases was significantly higher than matched primary carcinoma. NNMT was overexpressed in the stroma of primary and metastatic tumors. Increased NNMT expression was associated with decreased relapse-free and disease-specific survival. Conclusion This study detected a higher expression of NNMT in metastases of HGSC compared to matched primary and associated increased metastatic NNMT expression with decreased survival. Upregulation of NNMT in tumor stroma suggests it plays a role in desmoplasia. Targeting of NNMT and desmoplasia may play a critical role in the treatment of HGSC.