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Öğe BRAF mutation, TERT promoter mutation, and HER2 amplification in sporadic or neurofibromatosis-related neurofibromas and malignant peripheral nerve sheath tumors: do these molecules have a signature in malignant transformation?(Wiley, 2020) Coskun, Sinem; Gamsizkan, Mehmet; Yilmaz, Ismail; Yalcinkaya, Ulviye; Sungur, Mehmet Ali; Buyucek, Seyma; Onal, BinnurPeripheral nerve sheath tumors may occur sporadically or related to neurofibromatosis (NF). Unless the mechanisms of tumorigenesis in NF related malignant peripheral nerve sheath tumors (MPNST) are better understood, it remained unclear in sporadic cases. We aimed to investigate the genetic route for malignancy in both individuals with NF-1 and sporadic ones to open a way for targeted therapies in the future. We investigated the role of HER2 with Dual ISH DNA Probe Cocktail test, BRAF mutation (exon 15) and TERT promoter mutation frequency with Sanger sequencing method in respectively 25 sporadic neurofibromas, 25 NF-1 related neurofibromas and 25 MPNST cases from two institutes. Categorical data were analyzed and summarized as frequency and percentage. Statistical analysis was done with SPSS v.22 statistical package, and the statistical significance level was considered as 0.05. We identified TERT promoter mutation only in one sporadic MPNST (4%) and no BRAF mutation in any case. HER2 amplification is found in 10/25 (40%) MPNST cases. No mutations or gene amplification detected in neurofibromas (p < 0.001). MPNSTs are sarcomas with poor prognosis and limited treatment options. TERT promoter mutations and HER2 amplification may play a putative role in therapeutic purposes.Öğe 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, IsmailBackground/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.Öğe The Comparative Dermal Stimulation Potential of Constant-Volume and Constant-Amount Diluted Calcium Hydroxylapatite Injections Versus the Concentrated Form(Lippincott Williams & Wilkins, 2023) Botsali, Aysenur; Erbil, Hakan; Esme, Pelin; Gamsizkan, Mehmet; Aksoy, Ali Okan; Caliskan, ErcanINTRODUCTION Biostimulation properties of diluted and hyperdiluted calcium hydroxylapatite (CaHA) injections have become increasingly popular. However, the existing data are insufficient to certify a particular dose-response pattern.OBJECTIVE To assess and compare the dermal stimulation potentials of different concentrations of CaHA injections.MATERIALS AND METHODS Two independent experiments (Experiment-1: constant injection volume vs Experiment-2: constant CaHA amount) included 4 study groups each, and these experimental groups were placed consecutively on the abdominal skin of a juvenile Yorkshire pig. Histopathological and immunohistochemical stainings were performed on punch biopsy materials collected 4 months after the injection day.RESULTS The fibroblast count significantly decreased upon dilution from 1:3 to 1:19 in experiment 1 (p = .000) but still higher than the control group. In experiment 1, the collagen density of the concentrated form was more elevated than the 1:19 dilution and the negative control groups (p = .034 and .000, respectively) but similar to the 1:3 dilution (p = .123). No significant difference was observed between the groups regarding collagen density with a standard amount of CaHA (0.2 mL, 30%) (p > .05).CONCLUSION Despite the efficacy being more pronounced till 1:3 dilution, hyperdiluted CaHA at any dilution ratio up to 1:19 can provide a higher fibroblast count than the negative control group.Öğe Comparison of histopathological and biomechanical changes of ligamentum mucosum in patients with anterior cruciate ligament rupture(Turkish Joint Diseases Foundation, 2024) Turhan, Yalcin; Arican, Mehmet; Karaduman, Zekeriya Okan; Sungur, Mehmet Ali; Gamsizkan, MehmetObjectives: The aim of this study was to identify the biomechanical and histopathological changes of ligamentum mucosum (LM) in patients with intact versus ruptured anterior cruciate ligament (ACL). Patients and methods: A total of 67 patients (45 males, 22 females; mean age: 33.2 +/- 7.9 years; range, 18 to 45 years) who underwent arthroscopic knee surgery for intraarticular pathologies between July 2022 and January 2023 were prospectively analyzed. The patients with LM were divided into two groups as the ACL intact group (n=31) and ACL ruptured group (n=36). Biomechanical tests and histopathological examinations were performed in all LM patients. Results: Age and body mass index distributions were similar between the groups (p>0.05). Peak force values of the LM in the ACL ruptured group were significantly higher than the ACL intact group (p=0.037). No significant difference was found between the groups in terms of collagen index (p=0.103) and fibroblast count (p=0.821). Conclusion: The peak force values of the LM were significantly higher in the ACL ruptured group as compared to the ACL intact group, which is probably due to the adaptation of LM in patients with ACL rupture against increased deforming forces to maintain knee stability.Öğe Intraoperative Dermatoscopic Features of Subungual Exostosis(Mashhad Univ Med Sciences, 2020) Elmas, Omer Faruk; Kilitci, Asuman; Uyar, Belkiz; Gamsizkan, Mehmet[Abstract Not Available]Öğe Investigation of the Relationship of Two-Glass Test with Prostate Biopsy and Presence and Grade of Asymptomatic Prostate Inflammation in Men with Serum Prostate-Specific Antigen Level Between 2.5-10 ng/ml(Duzce Univ, Fac Medicine, 2024) Yuksel, Alpaslan; Tekin, Ali; Senoglu, Yusuf; Baba, Dursun; Gamsizkan, MehmetObjective: Prostate-specific antigen (PSA) is utilized as a marker to detect prostate cancer. Elevated PSA levels often lead to prostate biopsy to assess the potential presence of cancer. However, PSA elevation is not specific to cancer and can be caused by various conditions, including benign prostatic hyperplasia (BPH), urinary tract infections, and chronic prostatitis. Notably, approximately 66% of patients undergoing biopsy do not have prostate cancer, leading to unnecessary procedures and associated complications. Chronic prostatitis is detected in around 40% of these biopsies. The two-glass test involves examining urine before and after a rectal examination to diagnose chronic prostatitis. This study aims to investigate the effectiveness of the two-glass test in predicting prostatitis and inflammation in patients with PSA levels between 2.5-10 ng/ml who have undergone prostate needle biopsy. Materials and Methods: The study included fifty-two male patients aged between 50 and 78 years with PSA levels between 2.5 and 10 ng/ml who presented to our clinic. All patients underwent the EPS-two-glass test and prostate biopsy. EPS (expressed prostatic secretion) is obtained by collecting fluid from the urethra after prostate massage, while VB-3 (voided bladder-3) is urine collected after a massage. These samples are used to detect prostate infection. Prostate inflammation was deemed significant if >= 10 leukocytes were observed under the microscope. Patients were categorized into three groups based on pathology results: prostate cancer, BPH, and chronic prostatitis. The chronic prostatitis group was further classified based on histopathological calcification described by Nickel. Results: Chronic prostatitis was detected in 38% of the study participants. VB3 positivity was significantly higher in the chronic prostatitis group compared to the other groups (p = 0.028). Although no significant difference was observed in the prevalence of inflammation and PSA elevation, PSA levels were higher in the multifocal inflammation subgroup compared to the focal inflammation group. Conclusions: The relationship between chronic prostatitis and PSA elevation remains unclear. Although this study did not find a statistical relationship between inflammation and PSA elevation, the significant correlation between chronic prostatitis and VB3 positivity suggests a potential link. These findings can serve as a foundation for further research aimed at reducing unnecessary biopsies.Öğe KRAS, BRAF, PIK3CA mutation frequency of radical prostatectomy samples and review of the literature(Taylor & Francis Ltd, 2021) Bahcivan, Atike; Gamsizkan, Mehmet; Coskun, Sinem Kantarcioglu; Cangur, Sengul; Yuksel, Alpaslan; Ceyhan, Aysegul; Onal, BinnurObjective The molecular basis of prostate cancer is highly heterogeneous. Our study aimed to perform the mutation analysis of KRAS, BRAF, PIK3CA, and immunohistochemical (IHC) evaluation of EGFR, HER2, p16, and PTEN to demonstrate new areas for targeted therapies. Methods A total of 24 prostatectomy samples diagnosed with adenocarcinoma were analyzed by microarray hybridization. Also, these samples were IHC stained for EGFR, HER2, P16, and PTEN. The cases were divided into two groups based on low and high Gleason scores. All findings were compared with the clinicopathological parameters of the patients. Results While KRAS mutation was in 3/24 (12.5%) of our cases, BRAF and PIK3CA mutations were not detected. There was no significant difference between the groups in terms of KRAS mutation frequency. HER2 was immunohistochemically negative in all samples. There was no correlation between EGFR, P16 immunopositivity, and clinicopathological features. Conclusion KRAS mutation frequency is similar to those in Asian populations. BRAF and PIK3CA mutation frequencies have been reported in the literature in the range of 0-15% and 0-10.4%, respectively, consistent with our study findings. HER2 immunoexpression is a controversial issue in the literature. EGFR and p16 expressions may not correlate with the stage.Öğe Novel mutation identified in the DDB2 gene in patients with xeroderma pigmentosum group-E(Wiley, 2020) Karagun, Ebru; Eroz, Recep; Gamsizkan, Mehmet; Baysak, Sevim; Eyup, Yavuz; Ozcan, YunusBackground Xeroderma pigmentosum (XP) is a rare photosensitive syndrome, which is divided into eight complementation groups (XP-A to XP-G and XPV) and characterized by skin cancers diagnosed at early age. A family of seven members (age range between 5 and 47 years) with carriers of the novel nonsense mutation that causes XP-E type were included in the current study. Methods DNA was isolated from peripheral blood samples of the proband, and cancer predisposition genes were sequenced with next-generation sequencing. The demographic features and the laboratory, clinical, and histopathological findings of patients were evaluated. Results In the proband, squamous cell carcinoma was first diagnosed in the right-eye cornea at the age of 13 years and then in the left-eye cornea at the age of 15 years. Later, the patient was diagnosed with basosquamous cell carcinoma on the dorsum of the nose at the age of 18 years. After genetic analysis, a novel nonsense c.1063C>T(p.Arg355Ter) pathogenic variation that causes XP-E type was detected as homozygous in the DDB2 gene of the proband and her siblings, 11 and 5 years of age, and as heterozygous in her parents and a 22-year-old brother. Conclusion Because of the occurrence of early termination codon, truncated nonfunctional proteins or proteins with deleterious loss or gain-of-function activities are synthesized in nonsense mutation. Thus, to avoid the development of pathological lesions, it is important that such patients with nonsense mutation stay away from agents that might cause DNA damage and develop an appropriate lifestyle according to this condition.Öğe Refining diagnosis is the prerequisite for the correct treatment: The cytodiagnostic utility of SOX10 in the diagnosis of metastatic melanoma(Wiley, 2021) Kilitci, Asuman; Elmas, Omer Faruk; Demirbas, Abdullah; Gamsizkan, Mehmet; Atasoy, Mustafa; Tursen, Umit; Lotti, Torello[Abstract Not Available]Öğe Short- and long-term effects of rapamycin on ischemic damage and apoptotic changes in torsion of rat testes(Springer, 2021) Kabaklioglu, Murat; Kaya, Murat; Sahin, Ibrahim Ethem; Gamsizkan, Mehmet; Bahcivan, Atike; Eroz, RecepRapamycin has antioxidant defense mechanisms and immune suppressive effects. To detect the short- and long-term effects of rapamycin on ischemic damage and apoptotic changes in torsion of rat testes, mature male albino Wistar rats (n = 48) were included in the study as control, sham, early torsion-detorsion (T/D), early rapamycin treatment, early rapamycin control, late T/D, late rapamycin treatment, and late rapamycin control. The right testis was rotated 720 degrees in a clockwise direction during 4 h in operation groups. Rapamycin was administered orally three times: 30 min before detorsion and 24 and 48 h after detorsion. The animals were killed on the third day in early groups and on the tenth day in late groups after detorsion. Statistically significant differences among all groups were detected for SOD and TBARS, mean seminiferous tubule diameter (MSTD) and Cosentino's histologic score (CHS), caspase 3, bax, average number of apoptotic cells per tubule (ANPCT), and percentage of apoptotic tubule (PAT) values. ANPCT values were 10% lower in the rapamycin treatment groups compared with the untreated T/D groups, and the PAT values were also approximately 1.3 times lower. Although short-term usage of rapamycin may reduce to the tubular injury caused by I/R conversely to apoptosis in the testicular tissue after testicular torsion, rapamycin may have the potential to increase the long-term apoptosis with/without testicular torsion and a subsequent regression in fertility.Öğe Systemic tranexamic acid promotes bone healing in a rat model of femur fracture(Turkish Joint Diseases Foundation, 2020) Karaduman, Zekeriya Okan; Arican, Mehmet; Turhan, Yalcin; Turhal, Ozan; Orhan, Zafer; Gamsizkan, MehmetObjectives: This study aims to investigate the effect of tranexamic acid (TXA) on the union of closed femoral fractures using radiological and histological methods in an experimental rat model. Materials and methods: This experimental study was conducted between June 2017 and February 2018. Closed femoral fractures were created in 36 male Wistar albino rats (age: three months [range. 2.5-3.5 months]. weighing 200 grams [range. 180-220 grams]). Half of the animals randomly divided into two groups were administered intravenous single dose of TXA (30 mg/kg). whereas the animals in the control group did not receive any medication. The animals in the two groups were randomly divided into three groups with six animals each and cervical dislocation was performed at days 15, 30, and 45, and radiological and histopathological healing scores were compared. Results: When the mean radiological scores of the TXA and control groups were compared. a statistically significant difference was found in favor of the TXA group at day 15 (p=0.019). but no significant difference was found in the mean scores on days 30 and 45 (p=0.138 and p=0.269. respectively). Histopathological examination also showed a statistically significant difference between the 15-day mean score values in favor of the TXA group (p=0.017). Conclusion: The use of systemic TXA accelerates early bone formation and fracture healing.
