Tıp Fakültesi / Faculty of Medicine
Permanent URI for this collectionhttps://hdl.handle.net/11727/1403
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Item Clear Cell Carcinoma of the Uterine Cervix; An Unusual HPV-Independent Tumor: Clinicopathological Features, PD-L1 Expression, and Mismatch Repair Protein Deficiency Status of 16 Cases(TURKISH JOURNAL OF OBSTETRICS AND GYNECOLOGY, 2023) Bulutay, Pinar; Eren, Ozgur Can; Ozen, Ozlem; Haberal, Asuman Nihan; Kapucuoglu, NilgunObjective: Endocervical clear cell carcinoma (c-CCC) is a rare and HPV-independent adenocarcinoma type of cervix. Being usually resistant to conventional chemotherapy. Immunotherapy has recently been added as a preferred regimen as a second-line treatment option for programed cell death-ligand 1 (PD L1)-positive or mismatch repair (MMR) deficient cervical carcinomas. In this study, clinicopathological features, PD-L1 expression, and MMR deficiency status of c-CCCs were investigated. Materials and Methods: Sixteen c-CCC diagnosed cases were included in this study. PD-L1 expression was evaluated using two different PD-L1 clones (22C3 and SP263). MMR deficiency status of the cases was evaluated using four MMR proteins (MLH1, PMS2, MSH2, and MSH6). Results: Most of the c-CCC cases were presented as FIGO Stage I (68.75%). PD-L1 expression in either tumoral or tumor-infiltrating immune cells (TILs) was present in 62.5% (10/16) and 69% (11/16) of the 22C3 and SP263 clones, respectively. Most of the cases with high TIL density were also positive for PD-L1. The PD-L1 expression rate was less than 50% in most of the cases and 12.5% of the cases shared extensive PD-L1 staining. Overall, MMR deficiency was observed in 31.25% of the cases. Most of the MMR-deficient cases (80%) were PD-L1 positive. Conclusion: Although our study cohort is limited, we have shown that PD-L1 expression and MMR deficiency can be found in c-CCCs in variable degrees. These findings suggest that accompanying TIL density and MMR deficiency could be used as candidates for predicting PD-L1 positivity for c-CCCs. However, to indicate the clinical importance of these findings, objective treatment outcomes of cases treated with immunotherapy should be seen.Item A Case of Cerebral Tuberculosis After Liver Transplant and Literature Review(2014) Tunca, M. Zeyneb; Akcay, Eda Yilmaz; Moray, Gokhan; Ozen, Ozlem; Ozdemir, B. Handan; https://orcid.org/0000-0001-6831-9585; https://orcid.org/0000-0003-2498-7287; https://orcid.org/0000-0002-9082-1317; https://orcid.org/0000-0002-7528-3557; 24635807; AAK-1960-2021; AAE-1041-2021; AAK-4468-2021; X-8540-2019The risk of active tuberculosis is high in solid-organ recipients. We evaluated the clinical presentation of tuberculosis. Pulmonary locations were the most frequent, and extrapulmonary locations were rarely seen. Among extrapulmonary sites, intracranial tuberculosis is rare, with a few case reports reported in the literature. We report a case of 27-year-old man, who received deceased-donor liver transplant due to hepatitis B virus-related chronic liver failure. One month after the liver transplant, neurologic symptoms developed, then he had attacks of tonicclonic convulsions. Cerebral stereotactic needle biopsy of left temporal lobe was performed. Histopathologically gliosis, rare lymphocyte infiltration, and epithelioid histiocytes were seen. Histochemical staining by Ziehl Neelsen stain noted acid-fast resistant bacillus. The case was diagnosed as granulomatous inflammation which led to tuberculosis. In addition to antituberculosis therapy, he was given antiviral therapy for prophylaxis. During therapy, reactivation of hepatitis B virus was noted, and the recurrent diseases of hepatitis B virus-related viral hepatitis was diagnosed on serial biopsies. Ten months after transplant, he died from liver failure. Tuberculosis is a serious opportunistic infection in transplant recipients. The incidence of transplant recipients worldwide ranges from 0.35% to 15%. In nonrenal transplant, rejection within 6 months before the onset of tuberculosis and type of primary immunosuppressive regimen were predictors of tuberculosis infection occurring 12 months after transplant. The diagnosis and effective management of tuberculosis after transplant warnings recognition of the epidemiologic and clinical characteristics of tuberculosis in transplant recipients.Item Presence of Matrix Metalloproteinase-2 and Tissue Inhibitor Matrix Metalloproteinase-2 Gene Polymorphisms and Immunohistochemical Expressions in Intracranial Meningiomas(2014) Coven, Ilker; Ozer, Ozge; Ozen, Ozlem; Altinors, Nur; Sahin, Feride Iffet; https://orcid.org/0000-0001-6731-2461; https://orcid.org/0000-0001-7308-9673; https://orcid.org/0000-0001-7308-9673; 25259564; ITT-4755-2023; AAC-7232-2020; AAC-7232-2020Object. Meningiomas are benign extraaxial tumors with a slow progression. Some of them, in spite of being benign in nature, may show an aggressive progression pattern. To investigate the behavioral characteristics of meningiomas, researchers have studied matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), interstitial collagens, proteins, vascular endothelial growth factors (VEGF), and tumor necrosis factors. Methods. In this study, the authors investigated MMP2 and TIMP2 gene polymorphisms in formalin-fixed paraffin-embedded tissue samples obtained from meningioma patients who had previously undergone surgery at the authors' institution. In addition, brain invasion, Ki-67 index, and MMP-2 and TIMP-2 expressions were investigated using immunohistochemical methods. MMP2 (735C>T, 1575G>A, 1306C>T) and TIMP2 (418G>C, 303C>T) gene polymorphisms were investigated from paraffin-embedded tissue sections using the polymerase chain reaction restriction fragment length polymorphism method. Results. There were statistically significant differences between genotype (p = 0.001) and allele frequencies (p = 0.001 and OR 7.4 [95% CI 1.5-36.2]) in patient and control groups for MMP2 1306C>T polymorphism. The authors did not find a statistically significant difference for other polymorphisms. GA genotype was found to be more frequent when brain invasion was suspected for MMP2 1575G>A polymorphism (p = 0.006), There was not a statistically significant difference for other MMP2 or TIMP2 gene polymorphisms. Conclusions. The authors' results support the importance of MMPs and their tissue inhibitors in meningioma pathogenesis. In future studies, these gene polymorphisms, especially MMP2 1306C>T and 1575G>A, should be investigated for meningioma or brain invasion susceptibility in larger study groups.Item Clinicopathologic Features and the Loss of ARID1A Expression in Ovarian Seromucinous Borderline Tumors and Seromucinous Carcinomas(2023) Ok Atilgan, Alev; Ozen, Ozlem; Haberal Reyhan, A. Nihan; Ayhan, Ali; 36452965The current study highlighted the ARID1A and SALL4 expression and described histopathologic and immunohistochemical features of ovarian seromucinous tumors (SMTs) including borderline tumors (SMBTs) and seromucinous carcinomas (SMC; namely as endometrioid carcinoma with mucinous differentiation according to WHO 2020 classification). The clinicopathological and immunohistochemical features of 38 SMTs were analyzed, including ARID1A, SALL4, estrogen receptor (ER), progesterone receptor (PR), TP53, keratin 7, keratin 20, CEA, CDX2, WT1, PAX2, and PAX8. SMCs and SMBTs comprised 68.4% (n = 26) and 31.6% (n = 12) of all SMTs, respectively, studied. The mean age of diagnosis was 47.4 years and 41.4 years, and the mean size was 9 cm and 7.45 cm for SMC and SMBT, respectively. There was endometriosis or endometriotic cyst in 61.5% of SMCs and 50% of SMBTs. Immunohistochemically, loss of ARID1A staining was observed in 15 (65.2%) of 26 SMCs, and 3 (33.3%) of the 12 SMBTs. Only one SMC showed focal SALL4 positivity. All SMTs were positive for ER, PR, PAX8, and keratin 7. SMTs were negative for WT1, keratin 20, CDX2, and CEA (negative in 66.7% to 92.3% of the cases). While all SMBTs and 24 (92.3%) of 26 SMCs exhibited "wild-type" TP53 staining, 2 (7.7%) SMCs, both were stage III, showed mutant type TP53 overexpression. We indicate there is a similarity between SMC and SMBT according to the immunohistochemical features. SMBTs are keratin 7, ER, PR positive tumors, and some of them have loss of ARID1A expression and are likely to develop in the background of endometriosis similar to SMC.Item Reproducibility of Morphologic Parameters of the International Endocervical Adenocarcinoma Criteria and Classification System and Correlation With Clinicopathologic Parameters: A Multi-Institutional Study(2022) Bulutay, Pinar; Haberal, Nihan; Ozen, Ozlem; Erdem, Ozlem; Zeren, Emine H.; Kulac, Ibrahim; Taskiran, Cagatay; Vatansever, Dogan; Ayhan, Ali; Kapucuoglu, Nilgun; 34856570Endocervical adenocarcinomas (ECAs) have been recently reclassified according to their morphologic features linked to etiology by the International Endocervical Adenocarcinoma Criteria and Classification (IECC) and this system is adopted by WHO 2020. This classification separates the ECAs as human papillomavirus (HPV)-associated (HPVA) and HPV-independent (HPVI) subtypes. According to WHO 2020, high risk (HR)-HPV association can be histologically recognized by the presence of luminal mitoses and apoptosis. Therefore, investigating the reproducibility of the morphologic criteria of this new classification will be important in observing the recognizability of tumor types. Full slide sets of 94 ECAs were collected from 4 institutions in Turkey and reclassified on the basis of IECC/WHO 2020 criteria and the presence or absence of HR-HPV. HR-HPV presence was confirmed by HPV DNA in situ hybridization, p16 immunohistochemistry and in conflicted cases with real time-polymerase chain reaction. The final diagnoses were given based on the combination of the histologic evaluation and ancillary test results. Our cohort consisted of 73.4% HPVA and 26.6% HPVI cases. According to the WHO 2020 criteria 92.7% of HPVAs and 88% of HPVIs were easily classified. HPV DNA in situ hybridization was positive in 91.3% of the HPVAs and p16 was positive in all HPVAs, and also positive in 8% of the HPVIs. In conclusion, most of the ECAs can be diagnosed by their characteristic morphologic features by the WHO 2020 criteria. However, we want to emphasize that mitosis/apoptosis criteria may not be helpful especially in mucinous ECAs and ancillary tests for HR-HPV should be used in challenging cases.Item Clinicopathologic and Prognostic Significance of CD47 Expression and Tumor-associated Macrophages in Endometrial Carcinoma(2022) Sercan, Cigdem; Haberal Reyhan, Asuman N.; Ozen, Ozlem; Ayhan, Ali; 34282107Tumor-associated macrophages (TAMs) influence cancer progression. CD47 is an antiphagocytic molecule aiding tumor resistance against host immune surveillance. The relationship between CD47 expression and TAM-related microenvironment in endometrial carcinoma (EC) is poorly understood. The expression and prognostic significance of CD47 and CD163-labeled TAMs in 165 EC cases was assessed with CD47 and CD163 immunohistochemical studies. CD47 expression was found in 156/165 (94.6%) cases. CD47 expression was significantly higher in nonendometrioid carcinomas. CD47 overexpression was associated with histologic grade. High epithelial and stromal TAMs counts were also associated with high tumoral CD47 expression. High epithelial, stromal, and margin TAMs counts were associated with higher histologic grade and lymphovascular invasion. Epithelial TAMs counts were higher in patients with nonendometrioid carcinomas (P=0.0001) and cases with recurrence (P=0.018). High stromal TAMs counts were associated with deeper myometrial invasion (P=0.017) and the presence of distant metastasis (P=0.024). The counts of margin TAMs was significantly correlated with the depth of myometrial invasion, lymphovascular invasion, FIGO stage, lymph node metastases, distant metastasis, and recurrence (P=0.0001, 0.0001, 0.004, 0.005, 0.014, and 0.04, respectively). CD47 expression was not associated with overall survival (OS) and progression-free survival. However, high epithelial and stromal TAM counts were associated with shorter OS. Besides, high epithelial and margin TAM counts were associated with shorter progression-free survival. Furthermore, increased stromal and margin TAM counts were determined to be an independent prognostic marker of reduced OS. TAM count is, therefore, a significant prognostic factor in EC and the CD47 assessment has potential benefit for future clinical use.Item Androgenetic Alopecia or Fibrosing Alopecia in a Pattern Distribution: When to Perform Biopsy in Unusual Cases?(2022) Ozcan, Deren; Vural, Ayse Tuncer; Ozen, Ozlem; 35656261Item The Overexpression of Programmed Death-Ligand 2 in Uterine Adenosarcoma: Correlation with High-Grade Morphology, Mutant Type TP53 Expression and Clinical Outcomes(2023) Atilgan, Alev Ok; Akcay, Eda Yilmaz; Ozen, Ozlem; Haberal Reyhan, A. Nihan; Ayhan, Ali; 35466759Immunotherapy involving the programmed death-1 (PD-1)/the programmed death-ligand (PD-1/PD-L) blockade is an understudied tumor therapy approach in cases of adenosarcoma. PD-L1 and PD-L2, and tumor protein p53 (p53) were examined in 20 uterine adenosarcoma cases, and tumor-infiltrating lymphocytes and tumor-associated macrophages were counted in tumor tissue using immunohistochemistry. While CPS PD-L1 positivity with 1% and 10% cut-off values was observed in 40% and 10% of tumors, respectively, CPS PD-L2 positivity with 1%, 10% and 50% cut-off values was observed in 100%, 85% and 50% of the tumors, respectively. The CPS PD-L2 positivity with a 50% cut-off value was positively correlated with tumor grade and the presence of sarcomatous overgrowth and lymphovascular invasion (LVI) (p = 0.025, p = 0.025, and p = 0.025, respectively). Nine of 11 high-grade adenosarcomas and none of the low-grade adenosarcomas showed mutant type p53 expression (p = 0.000). However, PD-L1 expression and tumor-infiltrating immune cells did not correlate with clinicopathological parameters. The CPS PD-L2 positivity with a 50% cut-off value was also positively correlated with mutant type p53 expression (p = 0.024) and tumor-associated macrophages density (p = 0.024). The CPS PD-L2 positivity with a 50% cut-off value and mutant type p53 expression were associated with shorter disease-free survival and shorter overall survival. The high density of tumor-associated macrophages and low density of tumor-infiltrating lymphocytes were also associated with shorter disease-free survival and overall survival (p < 0.05).These results suggested that the CPS PD-L2 positivity with a 50% cut-off value, p53 mutation and tumor microenvironment played an essential role in the progression of uterine adenosarcomas.Item Cervical Spinal Ependymoma With Hemorrhage in a Renal Transplant Patient(2022) Sahinturk, Fikret; Dere, Umit Akin; Kirnap, Mahir; Sonmez, Erkin; Altinors, Nur; Ozen, Ozlem; Haberal, Mehmet; https://orcid.org/0000-0002-0471-3177; https://orcid.org/0000-0002-6678-6224; 30251937; AAI-7972-2021; N-1435-2014Ependymomas are the most common intramedullary spinal tumors in adults and constitute around 20% of all spinal tumors in adults. There are 3 subgroups of ependymomas according to World Health Organization classification: subependymoma or myxopapillary (grade 1), ependymoma (grade 2), and anaplastic (grade 3). Therapy for patients is aimed at safe and total surgical removal and, in selected cases, postoperative radiotherapy. Bleeding from a spinal ependymoma, with subsequent urgent surgery, is extremely rare. Here, we present a case of a renal transplant patient who had a cervical ependymoma. Although a considerable volume of peritumoral blood was observed during surgery, the patient had no neurologic deficits and no signs of deterioration.Item Two cases of fibrosing alopecia in a patterned distribution after coronavirus disease 2019(2021) Ozcan, Deren; Vural, Ayse Tuncer; Ozen, Ozlem; 0000-0002-7450-6886; 0000-0001-8770-5721; 34491674; AAQ-6649-2021; AAQ-4123-2021
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