Browsing by Author "Tokat, Fatma"

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A Review on Cutaneous and Musculoskeletal Manifestations of CLOVES Syndrome
(DOVE MEDICAL PRESS LTD, 2022-01-01) Durmaz, Emel Ozturk; Demircioglu, Deniz; Dikmen, Pinar Yalinay; Alanay, Yasemin; Alanay, Ahmet; Demirkesen, Cuyan; Tokat, Fatma; Karaarslan, Ercan
CLOVES syndrome is a novel sporadic mosaic segmental overgrowth syndrome, currently categorized under the canopy of PROS (PIK3CA-related overgrowth spectrum) disorders. All PROS disorders harbor heterozygous postzygotic activating somatic mutations involving the PIK3CA gene. As an upstream regulator of the PI3K/AKT/mTOR signal transduction pathway, activating mutations of PIK3CA gene commence in uncontrolled growth of cutaneous, vascular (capillaries, veins, and lymphatics), adipose, neural, and musculoskeletal tissues. The excessive growth is segmental, patchy, asymmetric, and confined to body parts affected by the mutation. The term `CLOVES' is an acronym denoting congenital lipomatous overgrowth, vascular malformations, epidermal nevi and spinal (scoliosis) and/ or skeletal anomalies. The syndrome is characterized by an admixture of overgrown tissues, derived mainly from mesoderm and neuroectoderm. Among PROS disorders, CLOVES syndrome represents the extreme end of the spectrum with massive affection of almost the entire body. The syndrome might judiciously be treated with medications hampering with the PI3K/AKT/mTOR signal transduction pathway. This article aims at reviewing the cutaneous and musculoskeletal manifestations of CLOVES syndrome, as the paradigm for PROS disorders. CLOVES syndrome and other PROS disorders are still misdiagnosed, underdiagnosed, underreported, and undertreated by the dermatology community.
Comparison of Two Different Antibody Clones of Programmed Cell Death Ligand 1 (PD-L1) with Immunohistochemical Method on Various Tumors
(KARE PUBL, 2020-01-01) Tokat, Fatma
Objectives: Programmed cell death ligand 1 (PD-L1) is the most important immune checkpoint protein in immune defense against tumors. PD-1/PD-L1 inhibitors are considered an option in cancer treatments. The evaluation of PD-L1 immunohistochemical staining is used as a biomarker to determine the decision and response of the use ofthese inhibitory drugs. There is a wide variety of clones and platforms for the PD-L1 antibody, and each pathology department uses different clones and platforms which causes confusion. Therefore, in this study, we evaluated the immunohistochemical staining of different clones in the same tumor. Methods: Overall, 90 cases comprising 47 lung, 11 breast, 9 colon, 6 stomach, and 7 pancreatic carcinomas and 10 other tumors were included in the study. Of these, 43 specimens were obtained by resection, 40 by tru-cut biopsy, and 7 by endoscopic biopsy. Sections prepared from formalin-fixed paraffin-embedded blocks were evaluated immunohistochemically with SP142 and SP263 clones. Results: In this study, we observed positive staining in 48.8\% (n=44) and negative staining in 51.2\% (n=46) among all cancers with SP263 clone, and positive staining in 33.3\% (n=30) and negative staining in 66.7\% with SP142 clone as well. This study also showed that compared to SP263, SP142 clone stained tumor cells less in lung, colon, stomach, pancreatic, and other carcinomas. Conclusion: In this study, we found different staining percentages for SP263 and SP142 in the same tumor. Pathologists conducting immunohistochemical studies for PD-L1 should indicate the staining percentages of tumors and the antibody clone they used in the reports. Meanwhile, oncologists should keep in mind which clone was stained, and that selecting SP142 is less positive to correct patients who can receive appropriate immunotherapy.
EML4-ALK-positive lung adenocarcinoma presenting an unusual metastatic pattern in a 29-year-old woman who is alive and well in her third year follow up: A case report
(ELSEVIER SCIENCE BV, 2017-01-01) Tokat, Fatma; Zeren, Handan; Barut, Pinar; Tansan, Sualp; Ince, Umit
Non-small cell lung cancer (NSCLC) is a frequent tumor entity with high mortality. Although several newly discovered chromosomal translocations and mutations opened new horizons for targeted therapy, literature still lacks large series of NSCLC with chromosomal abberations and their correlations with histological and clinical features. We present a case of echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation positive adenocarcinoma of the lung with an unusual metastatic pattern in a 29-year-old young woman. Conclusion: Young adult non-smoker female patients with an unexplained pleural effusion and signs of metastatic disease should alert the physicians straight away for all types of malignancies including lung cancer. Any skin lesions should be evaluated carefully, biopsies should be done to exclude metastasis in urgency. On the other hand, an uncommon clinical presentation of a lung cancer requires corresponding molecular testing rapidly in order to offer the best treatment option. (C) 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license.
Endometriosis of The Sigmoid Colon Mimicking Colon Cancer
(Acıbadem Mehmet Ali Aydınlar Üniversitesi, 2013-07-01) Merter, Gülen; Leventoğlu, Sezai; Menteş, B. Bülent; Tokat, Fatma; Demirhan, Beyhan; Duru, F. Bahattin; Yörübulut, Mehmet
ABSTRACT Endometriosis is one of the most common benign gynecological disorders in women of reproductive age. Intestinal involvement occurs in 3 to 37 percent of patients with pelvic endometriosis, usually affecting the rectosigmoid colon. Sometimes, the differential diagnosis of colorectal endometriosis from carcinoma of the colon and rectum is difficult due to similar colonoscopic and radiologic findings. We report a case of a 45-year-old woman presenting with intraabdominal mass and symptoms of bowel obstruction due to colonic endometriosis. An uneventful anterior resection of the sigmoid colon was performed. Histopathological examination of the resected colon revealed colonic endometriosis. This case demonstrates the difficulty of establishing an accurate pre-operative diagnosis and the ability of intestinal endometriosis to mimic colon cancer.
Expression of vascular endothelial growth factor in follicular cell-derived lesions of the thyroid: Is NIFTP benign or precancerous?
(TURKISH SURGICAL ASSOC, 2022-01-01) Kurtulmus, Neslihan; Tokat, Fatma; Duren, Mete; Kaya, Hakan; Ertas, Burak; Ince, Umit
Objective: Vascular endothelial growth factor (VEGF) is an angiogenic factor that plays an important role in physiological and pathological angiogenesis of the thyroid. The aim of the current study was to determine the expression characteristics of VEGF in follicular cell-derived lesions of the thyroid and to assess whether a new entity noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is precancerous. Material and Methods: Patients diagnosed with 33 follicular adenomas (FA), 41 invasive follicular variant papillary thyroid cancer (IN-FVPTC), and 40 NIFTP in surgical resection materials were evaluated retrospectively. Immunostaining was performed on 5-mu m paraffin tissue sections. The percentages of immunostaing for VEGF were evaluated on pathological materials. We used a percentage of labeled thyrocytes score (0, no labeling
Favorable locoregional control in clinically node-negative hormone-receptor positive breast cancer with low 21-gene recurrence scores: a single-institution study with 10-year follow-up
(BMC, 2022-01-01) Uras, Cihan; Cabioglu, Neslihan; Tokat, Fatma; Er, Ozlem; Kara, Halil; Korkmaz, Taner; Bese, Nuran; Ince, Umit
Background Recent studies have shown a lower likelihood of locoregional recurrences in patients with a low 21-gene recurrence score (RS). In this single-institution study, we investigated whether there are any associations between different cutoff values of 21-gene RS, histopathological factors, and outcome in patients with long-term follow-up. Methods The study included 61 patients who had early-stage (I-II) clinically node-negative hormone receptor-positive and HER2-negative breast cancer and were tested with the 21-gene RS assay between February 2010 and February 2013. Demographic, clinicopathological, treatment, and outcome characteristics were analyzed. Results The median age was 48 years (range, 29-72 years). Patients with high histologic grade (HG), Ki-67 >= 25\%, or Ki-67 >= 30\% were more likely to have intermediate/high RS (>= 18). Based on the 21-gene RS assay, only 19 patients (31\%) received adjuvant chemotherapy. At a median follow-up of 112 months, 3 patients developed locoregional recurrences (4.9\%), which were treated with endocrine therapy alone. Among patients treated with endocrine treatment alone (n = 42), the following clinicopathological characteristics were not found to be significantly associated with 10-year locoregional recurrence free survival (LRRFS): age < 40 years, age < 50 years, high histological or nuclear grade, high Ki-67-scores (>= 15\%, >= 20\%, >= 25\%, >= 30\%), presence of lymphovascular invasion, luminal-A type, multifocality, lymph node positivity, tumor size more than 2 cm, RS >= 18, and RS > 11. However, patients with RS >= 16 had significantly poorer 10-year LRRFS compared to those with RS < 16 (75\% vs. 100\%, respectively
Gamma-irradiated SARS-CoV-2 vaccine candidate, OZG-38.61.3, confers protection from SARS-CoV-2 challenge in human ACEII-transgenic mice
(NATURE PORTFOLIO, 2021-01-01) Turan, Raife Dilek; Tastan, Cihan; Kancagi, Derya Dilek; Yurtsever, Bulut; Karakus, Gozde Sir; Ozer, Samed; Abanuz, Selen; Cakirsoy, Didem; Tumentemur, Gamze; Demir, Sevda; Seyis, Utku; Kuzay, Recai; Elek, Muhammer; Kocaoglu, Miyase Ezgi; Ertop, Gurcan; Arbak, Serap; Elmas, Merve Acikel; Hemsinlioglu, Cansu; Ng, Ozden Hatirnaz; Akyoney, Sezer; Sahin, Ilayda; Kayhan, Cavit Kerem; Tokat, Fatma; Akpinar, Gurler; Kasap, Murat; Kocagoz, Ayse Sesin; Ozbek, Ugur; Telci, Dilek; Sahin, Fikrettin; Yalcin, Koray; Ratip, Siret; Ince, Umit; Ovali, Ercument
The SARS-CoV-2 virus caused the most severe pandemic around the world, and vaccine development for urgent use became a crucial issue. Inactivated virus formulated vaccines such as Hepatitis A and smallpox proved to be reliable approaches for immunization for prolonged periods. In this study, a gamma-irradiated inactivated virus vaccine does not require an extra purification process, unlike the chemically inactivated vaccines. Hence, the novelty of our vaccine candidate (OZG-38.61.3) is that it is a non-adjuvant added, gamma-irradiated, and intradermally applied inactive viral vaccine. Efficiency and safety dose (either 10(13) or 10(14) viral RNA copy per dose) of OZG-38.61.3 was initially determined in BALB/c mice. This was followed by testing the immunogenicity and protective efficacy of the vaccine. Human ACE2-encoding transgenic mice were immunized and then infected with the SARS-CoV-2 virus for the challenge test. This study shows that vaccinated mice have lowered SARS-CoV-2 viral RNA copy numbers both in oropharyngeal specimens and in the histological analysis of the lung tissues along with humoral and cellular immune responses, including the neutralizing antibodies similar to those shown in BALB/c mice without substantial toxicity. Subsequently, plans are being made for the commencement of Phase 1 clinical trial of the OZG-38.61.3 vaccine for the COVID-19 pandemic.
Has the COVID-19 Pandemic Affected Breast Cancer Stage and Surgical Volume?
(FRONTIERS MEDIA SA, 2022-01-01) Kara, Halil; Arikan, Akif Enes; Dulgeroglu, Onur; Tutar, Burcin; Tokat, Fatma; Uras, Cihan
BackgroundThis study investigates the effects of COVID-19 on the breast cancer stage and the volume of breast cancer surgery in a specialized breast institute. MethodsData of 332 patients who were diagnosed and treated for breast cancer between December 2019 and November 2020 were evaluated retrospectively according to periods of pandemic. ResultsA significant decrease in the number of operations, especially upfront surgeries rather than surgeries after neoadjuvant chemotherapy, was detected in the early period of the COVID-19 pandemic. It was found that patients with complaints were mostly admitted during this period (p = 0.024). No statistical significance was found for age, sex, side of the tumor, type of tumor, surgery to breast, and axilla. Following the early period of the pandemic, it was observed that patients with mostly luminal, early-stage, and less axillary nodal involvement (p < 0.05) were admitted, and as a result, it was founded that upfront surgeries increased, although no change in TNM staging was observed. However, it did affect the decision of initial treatment. Thus, the number of upfront surgeries was significantly higher than the NCT group (p = 0.027) following the early period. ConclusionSurgical volume is significantly affected in the early period of the COVID-19 pandemic. To overcome overload due to delayed surgeries related to pandemics, some hospitals should be spared for oncological treatments. Following the early period, mostly luminal type, early-stage patients were admitted, probably because of increased self-awareness and short wave duration, but the breast cancer stage was not affected.
Immune Thrombocytopenia in a Child with Neuroblastoma
(HINDAWI LTD, 2017-01-01) Ikizoglu, Hasan Tarkan; Ayan, Inci; Tokat, Fatma; Tecimer, Tulay; Tekant, Gonca Topuzlu
Thrombocytopenia is a frequent finding in patients with solid tumors. It is usually caused by bone marrow infiltration or by myelosuppression due to anticancer therapy
Immunoreactivity of Wilms tumor 1 (WT1) as an additional evidence supporting hemangiomatous rather than inflammatory origin in the etiopathogenesis of angiolymphoid hyperplasia with eosinophilia
(INT DERMOSCOPY SOCIETY, 2018-01-01) Tokat, Fatma; Lehman, Julia S.; Sezer, Engin; Cetin, Emel Dikicioglu; Ince, Umit; Durmaz, Emel Ozturk
Background: Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare vascular proliferative disorder mainly located in the periauricular region. The etiopathogenesis of ALHE is unknown, and it is still controversial as to whether the entity represents a benign vascular neoplasm or an inflammatory process. Aim: Recently, the intracytoplasmic staining pattern of Wilms tumor 1 (WT1) on immunohistochemistry has highlighted true vascular neoplasms, such as microvenular hemangioma, tufted angioma, and spindle cell hemangioma, which has made it helpful to distinguish ALHE from vascular malformations, as there is a negative staining pattern in the other entities. We aimed to investigate the immunoreactivity of ALHE specimens for WT1 as well as glucose transporter protein 1 (GLUT1) immunohistochemistry, an important and sensitive marker for the diagnosis of infantile hemangioma, which recently has been described to label other hemangiomas, such as verrucous hemangioma. Material and methods: Clinical data and histopathological specimens from patients diagnosed with ALHE were reviewed, and immunohistochemical staining and microscopic analysis for WT-1 and GLUT1 were performed. Results: Intracytoplasmic endothelial staining of WT1 was detected in 19 of 20 ALHE specimens. GLUT1 was not detected in any ALHE specimen. Conclusions: We conclude that ALHE may represent a true hemangioma (i.e., benign vascular neoplasia) characterized by an eosinophil- and lymphocyte-rich inflammatory component as opposed to the reactive inflammatory dermatosis with a positive intracytoplasmic staining pattern for WT1. As far as we are aware, WT1 staining for ALHE has not been described to date.
IRF4-Rearranged Large B-Cell Lymphoma on Waldeyer's Ring: A Case Report
(GALENOS YAYINCILIK, 2020-01-01) Buyuktas, Deram; Ornek, Serdar; Tokat, Fatma; Tecimer, Tulay; Ferhanoglu, Burhan
Laringeal Leiomiyosarkoma
(AVES, 2018-01-01) Ertas, Burak; Ozdilek, Alper; Onerci Altunay, Zeynep; Tokat, Fatma; Veyseller, Bayram
A laryngeal leiomyosarcoma is a very rare tumor that originates from heterotopic mesenchymal tissues or smooth muscle cells. It is diagnosed by immunohistochemical staining.
MITNET: a novel dataset and a two-stage deep learning approach for mitosis recognition in whole slide images of breast cancer tissue
(SPRINGER LONDON LTD, 2022-01-01) Cayir, Sercan; Solmaz, Gizem; Kusetogullari, Huseyin; Tokat, Fatma; Bozaba, Engin; Karakaya, Sencer; Iheme, Leonardo Obinna; Tekin, Eren; Yazici, Cisem; Ozsoy, Gulsah; Ayalti, Samet; Kayhan, Cavit Kerem; Ince, Umit; Uzel, Burak; Kilic, Onur
Mitosis assessment of breast cancer has a strong prognostic importance and is visually evaluated by pathologists. The inter, and intra-observer variability of this assessment is high. In this paper, a two-stage deep learning approach, named MITNET, has been applied to automatically detect nucleus and classify mitoses in whole slide images (WSI) of breast cancer. Moreover, this paper introduces two new datasets. The first dataset is used to detect the nucleus in the WSIs, which contains 139,124 annotated nuclei in 1749 patches extracted from 115 WSIs of breast cancer tissue, and the second dataset consists of 4908 mitotic cells and 4908 non-mitotic cells image samples extracted from 214 WSIs which is used for mitosis classification. The created datasets are used to train the MITNET network, which consists of two deep learning architectures, called MITNET-det and MITNET-rec, respectively, to isolate nuclei cells and identify the mitoses in WSIs. In MITNET-det architecture, to extract features from nucleus images and fuse them, CSPDarknet and Path Aggregation Network (PANet) are used, respectively, and then, a detection strategy using You Look Only Once (scaled-YOLOv4) is employed to detect nucleus at three different scales. In the classification part, the detected isolated nucleus images are passed through proposed MITNET-rec deep learning architecture, to identify the mitosis in the WSIs. Various deep learning classifiers and the proposed classifier are trained with a publicly available mitosis datasets (MIDOG and ATYPIA) and then, validated over our created dataset. The results verify that deep learning-based classifiers trained on MIDOG and ATYPIA have difficulties to recognize mitosis on our dataset which shows that the created mitosis dataset has unique features and characteristics. Besides this, the proposed classifier outperforms the state-of-the-art classifiers significantly and achieves a 68.7\% F1-score and 49.0\% F1-score on the MIDOG and the created mitosis datasets, respectively. Moreover, the experimental results reveal that the overall proposed MITNET framework detects the nucleus in WSIs with high detection rates and recognizes the mitotic cells in WSI with high F1-score which leads to the improvement of the accuracy of pathologists' decision.
Multi-center real-world comparison of the fully automated Idylla (TM) microsatellite instability assay with routine molecular methods and immunohistochemistry on formalin-fixed paraffin-embedded tissue of colorectal cancer
(SPRINGER, 2021-01-01) Velasco, Ana; Tokat, Fatma; Bonde, Jesper; Trim, Nicola; Bauer, Elisabeth; Meeney, Adam; de Leng, Wendy; Chong, George; Dalstein, Veronique; Kis, Lorand L.; Lorentzen, Jon A.; Tomic, Snjezana; Thwaites, Keeley; Putzova, Martina; Birnbaum, Astrid; Qazi, Romena; Primmer, Vanessa; Dockhorn-Dworniczak, Barbara; Hernandez-Losa, Javier; Soares, Fernando A.; Gertler, Asaf A.; Kalman, Michal; Wong, Chris; Carraro, Dirce M.; Sousa, Ana C.; Reis, Rui M.; Fox, Stephen B.; Fassan, Matteo; Brevet, Marie; Merkelbach-Bruse, Sabine; Colling, Richard; Soilleux, Elizabeth; Teo, Ryan Yee Wei; D'Haene, Nicky; Nolet, Serge; Ristimaki, Ari; Vaisanen, Timo; Chapusot, Caroline; Soruri, Afsaneh; Unger, Tina; Wecgowiec, Johanna; Biscuola, Michele; Frattini, Milo; Long, Anna; Campregher V, Paulo; Matias-Guiu, Xavier
Microsatellite instability (MSI) is present in 15-20\% of primary colorectal cancers. MSI status is assessed to detect Lynch syndrome, guide adjuvant chemotherapy, determine prognosis, and use as a companion test for checkpoint blockade inhibitors. Traditionally, MSI status is determined by immunohistochemistry or molecular methods. The Idylla (TM) MSI Assay is a fully automated molecular method (including automated result interpretation), using seven novel MSI biomarkers (ACVR2A, BTBD7, DIDO1, MRE11, RYR3, SEC31A, SULF2) and not requiring matched normal tissue. In this real-world global study, 44 clinical centers performed Idylla (TM) testing on a total of 1301 archived colorectal cancer formalin-fixed, paraffin-embedded (FFPE) tissue sections and compared Idylla (TM) results against available results from routine diagnostic testing in those sites. MSI mutations detected with the Idylla (TM) MSI Assay were equally distributed over the seven biomarkers, and 84.48\% of the MSI-high samples had >= 5 mutated biomarkers, while 98.25\% of the microsatellite-stable samples had zero mutated biomarkers. The concordance level between the Idylla (TM) MSI Assay and immunohistochemistry was 96.39\% (988/1025)
Preclinical Assessment of Efficacy and Safety Analysis of CAR-T Cells (ISIKOK-19) Targeting CD19-Expressing B-Cells for the First Turkish Academic Clinical Trial with Relapsed/Refractory ALL and NHL Patients
(GALENOS YAYINCILIK, 2020-01-01) Tastan, Cihan; Kancagi, Derya Dilek; Turan, Raife Dilek; Yurtsever, Bulut; Cakirsoy, Didem; Abanuz, Selen; Yilanci, Muhammet; Seyis, Utku; Ozer, Samed; Mert, Selin; Kayhan, Cavit Kerem; Tokat, Fatma; Elmas, Merve Acikel; Birdogan, Selcuk; Arbak, Serap; Yalcin, Koray; Sezgin, Aslihan; Kizilkilic, Ebru; Hemsinlioglu, Cansu; Ince, Umit; Ratip, Siret; Ovali, Ercument
Objective: Relapsed and refractory CD19-positive B-cell acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) are the focus of studies on hematological cancers. Treatment of these malignancies has undergone recent transformation with the development of new gene therapy and molecular biology techniques, which are safer and well-tolerated therapeutic approaches. The CD19 antigen is the most studied therapeutic target in these hematological cancers. This study reports the results of clinical-grade production, quality control, and in vivo efficacy processes of ISIKOK-19 cells as the first academic clinical trial of CAR-T cells targeting CD19-expressing B cells in relapsed/refractory ALL and NHL patients in Turkey. Materials and Methods: We used a lentiviral vector encoding the CD19 antigen-specific antibody head (FMC63) conjugated with the CD8-CD28-CD3 zeta
Primary pericardial extragastrointestinal stromal tumor: A case report and literature review
(SPANDIDOS PUBL LTD, 2015-01-01) Arpaci, Taner; Tokat, Fatma; Arpaci, Rabia Bozdogan; Akbas, Tugana; Ugurluer, Gamze; Yavuz, Sinan
Gastrointestinal stromal tumors (GISTs) are the most prevalent mesenchymal tumors of the gastrointestinal tract. GISTs are considered to originate from the interstitial cells of Cajal, the pacemakers of the peristaltic activity of the gastrointestinal tract. More than 95\% of GISTs express KIT protein and discovered on GIST-1. GISTs may also be encountered in locations outside the gastrointestinal tract, in which case they are referred to as extra-GISTs (EGISTs) and often behave more aggressively. This is the case report of a primary pericardial EGIST in a 53-year-old male patient, confirmed by immunohistochemistry. To the best of our knowledge, this is the third case of EGIST diagnosed above the diaphragm, without being associated with the esophageal wall. Two cases of primary EGIST arising from the pleura were reported previously. In addition, this is the first reported case of an EGIST originating from the pericardium.
Three Cases of Breast Metastases from Lung Cancer and Systematic Review of the Literature
(GALENOS YAYINCILIK, 2021-01-01) Guldogan, Nilgun; Icten, Gul Esen; Tokat, Fatma; Tutar, Burcin; Kara, Halil; Korkmaz, Taner; Uluc, Basak Oyan; Demir, Gokhan
Despite the high prevalence of lung cancer among other primary tumors, metastasis of this particular malignancy in the breast is very rare. We report three new cases of lung cancer with breast metastases and discuss radiological and clinical findings. Radiologically, each case displayed different characteristics. First, one of them had bilateral superficially and deeply located irregular lesions. Second, the patient presented with findings similar to inflammatory breast cancer. The third case had a circumscribed mass, resembling a benign complicated cyst. To guide clinicians for proper patient management, radiologists should be aware of the scope of typical and atypical imaging findings of metastatic involvement of the breast.