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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.
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    Prognostic significance of solid growth in endometrioid endometrial adenocarcinoma
    (SPRINGER JAPAN KK, 2020) Akar, Serra.; Çelik, Zeliha Esin.; Fındık, Sıddıka.; İlhan, Tolgay Tuyan.; Ercan, Fedi.; Çelik, Çetin.
    Background Endometrioid endometrial cancer is the most common histological subtype of endometrial adenocarcinoma. In the FIGO grading scheme, both architectural and nuclear grade are taken into consideration. However, the specific impact of solid growth alone on endometrioid endometrial adenocarcinoma outcome is not well documented. We sought to assess the degree of impact of solid growth on lymphovascular space invasion (LVSI), myometrial invasion, tumor size, FIGO stage, lymph node metastasis (LNM), relapse-free survival (RFS) and disease-specific survival (DSS). Methods Paraffin blocks of 269 patients treated for endometrioid endometrial cancer were retrospectively analyzed with morphometry for solid growth percentages. Results A statistically significant cut-off value of 1% solid growth was found for predicting LNM and advanced stage (III or IV), myometrial invasion and LVSI (p < 0.001) and a cut-off value of 8% was found for predicting adverse survival outcome (p < 0.001). The mean DSS was significantly higher in patients with < 6% solid growth compared to patients with 6-50%, 51-75% and > 75% solid growth (p < 0.001). Although, the mean RFS and DSS were lowest in patients with 51-75% solid growth, this did not reach statistical significance in comparison to 6-50% and > 75% (p > 0.05). Conclusion Although > 75% solid growth was most significantly associated with many of the adverse prognostic factors, this subset did not provide prognostic superiority in predicting adverse survival when compared to subsets within 6-75% solid growth. In conclusion, although no statistically significant difference in survival was found among subdivisions of architectural grades 2 and 3, solid growth, especially >= 8%, appeared to be an independent prognostic factor for survival in patients with early-stage endometrioid endometrial cancer.