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    Clinicopathologic Features and Prognostic Significance of Immunohistochemistry and In Situ Hybridization Based Molecular Classification in Gastric Carcinoma
    (Begell House Inc, 2023) Issin, Gizem; Sayar, Ilyas; Demir, Fatih; Bakkaloglu, Irem Guvendir; Gamsizkan, Mehmet; Yildiz, Zeliha; Yilmaz, Ismail
    Background/Aim: Gastric carcinoma (GC) is a highly heterogeneous disease with many subtypes that have different morphologic and molecular characteristics. In the current study, we analyzed immunohistochemical (IHC) and in situ hybridization (ISH) features of GCs and evaluated their association with prognosis and clinicopathological features. Materials and Methods: Three hundred cases analyzed by IHC and ISH for microsatellite stability, p53, e-cadherin, HER2, PD-L1 expression, and Epstein-Barr virus (EBV) status. Cases were classified into five subgroups based on expression profile. The relationships between subgroups, clinicopathological features, and survival were determined. Results: Ten ( 3.3%) cases were classified as EBV-associated, 45 (15%) as microsatellite instable (MSI), 73 (24.3%) as EBV-/ microsatellite-stable (MSS)/epithelial-mesenchymal-transformation (EMT)-like, 75 (25%) as EBV-/MSS/ non-EMT-like/p53+, and 97 (32.3%) as EBV-/MSS/non-EMT-like/ p53-. The MSI subtype had the best overall survival (OS). In contrast, the EBV-/MSS/EMT-like subtype had the poorest OS. The MSI subtype was also related with old age of the patient and antrum-corpus localized tumors, whereas the EBV-/MSS/EMT-like was associated with young age, larger tumor size, and advanced stage presentation. PD-L1 positivity is highly correlated with MSI and EBV-associated subtypes. Conclusion: Our data demonstrated a link between IHC/ISH characteristics of GC and clinical outcomes. IHC/ISH based molecular classification may be helpful in predicting the survival.
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    The effect of peripheral dopamine on fracture healing: an experimental study in a rat model
    (Bmc, 2025) Yucel, Mucahid Osman; Dalaslan, Rasit Emin; Saglam, Sonmez; Arican, Mehmet; Karaduman, Zekeriya Okan; Turhan, Banu; Demir, Fatih
    BackgroundDopamine is a versatile biomolecule that functions as a neurotransmitter, hormone, and immune modulator in the body. Although some anabolic effects of dopamine on bone tissue have been described in the literature, its influence on the complex processes involved in fracture healing remains unclear. This study aimed to evaluate the effects of dopamine on bone healing at the peripheral level.MethodsThirty-six male Wistar albino rats were randomly assigned to two groups: a control group with no treatment and a dopamine group that received 12 mg/kg levodopa twice daily via oral gavage following surgery. A standardized femoral fracture was induced under anesthesia in all the rats, which were then fixed with an intramedullary Kirschner wire. Each group consisted of 18 rats, and six rats from each group were randomly sacrificed on postoperative days 15, 30, and 45. The harvested femurs were first evaluated radiologically, followed by biomechanical analysis via a three-point bending test, and finally subjected to histopathological examination.ResultsNo significant differences were observed between the groups on days 15 and 30. However, on day 45, histopathological scores were significantly lower in the dopamine group (p = 0.015), and biomechanical strength was also lower (p = 0.004). Radiological scores were not significantly different between the groups at any time point.ConclusionDespite the known anabolic effects of dopamine on bone cells, it may adversely affect fracture healing. The negative impact of dopamine on bone union could be attributed to the multifactorial and complex nature of fracture healing, the dynamics of inflammatory processes, and the cumulative effects of various dopamine receptor subtypes.
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    EZH2 expression in colorectal carcinoma: an evaluation of clinicopathological and prognostic value
    (Springer, 2025) Cagatay, Diren Vuslat; Balci, Mecdi Gurhan; Issin, Gizem; Demir, Fatih
    BackgroundEnhancer of zeste homolog 2 (EZH2), the catalytic subunit of Polycomb Repressive Complex 2, catalyzes trimethylation of histone H3 lysine 27 and has been implicated in tumor progression.AimOur study aims to assess the relationship between EZH2 expression and clinicopathologic data, and survival in colorectal carcinomas (CRC).Materials and methodsEZH2 immunohistochemistry was performed on tumor blocks from 124 CRC patients. Based on H-scores, cases were stratified into low- and high-expression groups. EZH2 status was correlated with demographic, clinical, and pathologic features, and overall survival was analyzed with the Kaplan-Meier method and log-rank test.ResultsA total of 124 cases of CRC; 12 (9.7%) cases were classified as low EZH2 expression, and 112 (90.3%) cases were classified as high EZH2 expression. A significant association was found between EZH2 expression and microsatellite stability. High EZH2 expression was significantly enriched in microsatellite-stable tumors (p = 0.007) and in left-sided lesions (p = 0.049). No significant associations were detected with sex, stage, grade, lymph-node status, or vascular invasion. Kaplan-Meier analysis revealed no difference in overall survival between low- and high-EZH2 groups (log-rank p = 0.47; hazard ratio = 1.13, 95% CI 0.45-2.85). EZH2 staining was uniformly strong in normal mucosa and adenomas, mirroring the high expression observed in most CRCs.ConclusionsEZH2 is highly expressed across the normal-adenoma-carcinoma sequence and, in our cohort, was not linked to overall survival or to most clinicopathologic parameters in CRC. The lower expression observed in a subset of MSI-H tumors warrants further investigation; present evidence remains insufficient to establish EZH2 as an independent prognostic biomarker.