Browsing by Author "Ozen, Ozlem"

Now showing 1 - 20 of 23

Androgenetic Alopecia or Fibrosing Alopecia in a Pattern Distribution: When to Perform Biopsy in Unusual Cases?
(2022) Ozcan, Deren; Vural, Ayse Tuncer; Ozen, Ozlem; 35656261
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-8540-2019
The 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.
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-1435-2014
Ependymomas 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.
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, Nilgun
Objective: 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.
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; 34282107
Tumor-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.
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; 36452965
The 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.
Cloacogenic Adenocarcinoma of the Vulva: A Case Report and Review of the Literature
(2018) Tepeoglu, Merih; Uner, Halit; Haberal, Asuman Nihan; Ozen, Ozlem; Kuscu, Esra; 28272666
Primary adenocarcinoma of the vulva, unrelated to the native glands of perineum is an extremely rare neoplasm. Despite awareness of this lesion for over 40 years, the origin is not beyond speculation. The most reasonable hypothesis is based on the remnants of cloacal differentiation during early days of life. Here we report the case of a 60-year-old patient with a vulvar mass, who underwent partial vulvectomy and bilateral regional lymph node dissection. The tumor was composed of papillary and complex glandular structures and exhibited diffuse positivity for cytokeratin 20 and polyclonal CEA, CDX2, and focal positivity with cytokeratin 7. Unlike the indolent behavior of this malignant neoplasm according to the literature, we found two metastatic inguinal lymph nodes. She did not receive adjuvant therapy and is still alive, free of disease 38 months after surgery. We present different aspects of vulvar adenocarcinomas with a case report.
Diagnostic value of histopathologic examination in alopecias
(2014) Ozcan, Deren; Ozen, Ozlem; Seckin, Deniz
Alopecias are evaluated in two groups, namely noncicatricial type and cicatricial type. Cicatricial alopecias are generally irreversible due to the permenant damage to the hair follicles and as follicular epithelium is replaced by connective tissue in the late stages. In noncicatricial alopecia, the follicular epithelia is intact and hair regrowth is likely. The accurate diagnosis of alopecia subtypes which have different etiologies and occasionally result in permanent hair loss is of paramount importance to initiate the appropriate treatment in the early stages. Most of the subtypes of alopecia can be diagnosed with a detailed history and clinical evaluation. However, most of the disorders leading to alopecia present with nonspecific and overlapping clinical findings which alter over the course of the disease. In those instances, scalp biopsy and histopathologic evaluation is necessary to make or confirm the diagnosis. Transverse and vertical sections used for the interpretation of scalp biopsy specimens offer different advantages. Therefore, idealy, obtaining two 4 mm punch biopsy samples and combining both methods is suggested to enhance the diagnostic yield in patients with alopecia. In this review, the value of scalp biopsy in the diagnosis of subtypes of alopecia, the significance of evaluation of transverse and vertical sections in the histopathologic examination and the major histopathologic findings of the disorders involved in the etiology are described.
Effect of Topical Platelet-Rich Plasma on Burn Healing After Partial-Thickness Burn Injury
(2016) Ozcelik, Umit; Ekici, Yahya; Bircan, Huseyin Yuce; Aydogan, Cem; Turkoglu, Suna; Ozen, Ozlem; Moray, Gokhan; Haberal, Mehmet; 27262706
Background: To investigate the effects of platelet-rich plasma on tissue maturation and burn healing in an experimental partial-thickness burn injury model. Material/Methods: Thirty Wistar albino rats were divided into 3 groups of 10 rats each. Group 1 (platelet-rich plasma group) was exposed to burn injury and topical platelet-rich plasma was applied. Group 2 (control group) was exposed to burn injury only. Group 3 (blood donor group) was used as blood donors for platelet-rich plasma. The rats were killed on the seventh day after burn injury. Tissue hydroxyproline levels were measured and histopathologic changes were examined. Results: Hydroxyproline levels were significantly higher in the platelet-rich plasma group than in the control group (P=.03). Histopathologically, there was significantly less inflammatory cell infiltration (P=.005) and there were no statistically significant differences between groups in fibroblast development, collagen production, vessel proliferations, or epithelization. Conclusions: Platelet-rich plasma seems to partially improve burn healing in this experimental burn injury model. As an initial conclusion, it appears that platelet-rich plasma can be used in humans, although further studies should be performed with this type of treatment.
Good Outcomes of Patients with Stage IB Endometrial Cancer with Surgery Alone
(2014) Rahatli, Samed; Dizdar, Omer; Kucukoztas, Nadire; Oguz, Arzu; Yalcin, Selim; Ozen, Ozlem; Reyhan, Nihan Haberal; Tarhan, Cagla; Yildiz, Ferah; Dursun, Polat; Altundag, Ozden; Ayhan, Ali
Background: Most patients with endometrial cancer have stage I disease. Adjuvant therapy in stage IB (formerly IC) endometrial cancer is controversial, treatment options including observation or brachytherapy/radiotherapy in grade 1-3 patients with or without chemotherapy. The purpose of this study was to assess the outcomes of our patients with stage IB endometrioid endometrial cancer. Materials and Methods: Sixty two patients with stage IB endometrial cancer and endometrioid histology were retrospectively evaluated. All patients were initially treated surgically by the same surgeon with comprehensive staging, i.e. total abdominal hysterectomy, bilateral salphingooopherectomy, bilateral pelvic and paraaortic lymph node dissection and omentectomy. Adjuvant radiotherapy was discussed with patients and utilized by those who accepted. Adjuvant chemotherapy was not given to any of the patients. Results: Median age was 62 (range, 42-95). Ninety percent of the patients had grade 1-2 disease. Thirteen patients (21%) received intra vaginal brachytherapy (IVBT) and one received whole pelvic radiotherapy (WPRT). Median follow-up time was 46 months (range, 9-77 months). Three patients experienced recurrence (4.8%), two of them died on follow-up and one was still alive at last visit. Two patients with recurrence had FIGO grade 2 tumors and one had a grade 3 tumor. Two patients (3.2%) died without evidence of recurrent disease. Relapse free survival at 5 years was 94.4% and overall survival was 93.1%. Conclusions: Patients with stage IB disease in our study demonstrated relatively low recurrence rates with this stage of endometrial cancer.
Lichen planopilaris: Demographic, clinical and histopathological characteristics and treatment outcomes of 25 cases
(2015) Ozcan, Deren; Seckin, Deniz; Gulec, A.Tulin; Ozen, Ozlem; 0000-0002-7450-6886; 0000-0002-9082-1317; AAQ-6649-2021; AAK-4468-2021
Background and Design: Lichen planopilaris (LPP) is a type of cicatricial alopecia characterized by autoreactive lymphocytic destruction of the hair follicle. We aimed to evaluate the demographic, clinical and histopathological features, and treatment outcomes of patients with LPP. Materials and Methods: Medical reports of 25 patients, who have been diagnosed with LPP according to the clinical and histopathological findings between January 2006 and June 2012, were retrospectively reviewed. The transverse and vertical sections of scalp biopsy specimens were re-evaluated by a pathologist, and the findings were noted. Results: Of the 25 patients, 18 were female and 7 were male, the mean age was 49.8 +/- 12.4 years. Eighteen patients had been diagnosed with classic LPP and 7 patients with frontal fibrosing alopecia (FFA). The alopecia has begun in postmenopausal period in 5 patients with FFA. Alopecia was associated with pruritus, pain and/or burning in 19 patients. Extra-scalp involvement was observed in 11 patients. The most common clinical findings were follicular hyperkeratosis (92%), perifollicular erythema (48%), perifollicular lichenoid papules, and positive hair-pull test (44%). Dermatoscopic examination was performed in 14 patients, and most commonly, absence of follicular openings (100%), perifollicular scales (92.9%) and perifollicular erythema (50%) were noted. The most common diagnostic histopathological findings were follicular vacuolar and lichenoid degeneration (88%) and vacuolar and lichenoid interface changes (56%). Twenty-three patients who were started on treatment received topical, intramuscular and intralesional corticosteroids, topical minoxidil, oral tetracycline, cyclosporine A, and hydroxychloroquine either alone or in combination. Progression of alopecia was prevented and the symptoms and/or signs were reduced in 12 (75%) of 16 patients whose follow-up data were available. Conclusion: LPP can be diagnosed accurately through a detailed clinical examination, dermatoscopy and histopathological examination. The symptoms and/or signs can be reduced and progression of the disease can be prevented with treatment.
Microsatellite Instability in Glioblastoma: Is It Really Relevant in Tumor Prognosis?
(2019) Tepeoglu, Merih; Borcek, Pelin; Ozen, Ozlem; Altinors, Nur; 31529454
AIM: To evaluate the frequency and prognostic significance of microsatellite instability (MSI) in patients with glioblastoma (GBM immunohistochemical analysis of mismatch repair (MMR) proteins was performed. MATERIAL and METHODS: A total of 71 patients with GBM who underwent surgery between 2011 and 2019, were included in the study. MMR protein expression was examined using immunohistochemistical analysis of tumor tissue samples; the association between the MMR status and clinicopathological findings was evaluated. RESULTS: Immunohistochemical analysis revealed expressions of MLH1, MSH2, MSH6, and PMS2 proteins in 67 (94.4%), 65 (91.5%), 67 (94.4%), and 64 (90.1%) patients, respectively. Among the 71 patients, 64 (90.1%) expressing all MMR proteins were considered microsatellite stable (MSS), and 7 (9.9%) patients showing loss of at least one of the MMR proteins were considered to show MSI. Tumor recurrence was noted in 25 (39.1%) patients in the MSS GBM group, and 4 (57.1%) patients in the MSI GBM group (p=0.433). The overall median survival was 30.65 +/- 5.1 and 10.71 +/- 5.2 months in the MSS GBM and MSI GBM groups, respectively (p=0.059). CONCLUSION: The results of this study showed no significant relationships between MMR protein expression and recurrence rates or overall survival in patients with GBM.
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; 35466759
Immunotherapy 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.
Platelet-rich plasma for treatment resistant frontal fibrosing alopecia: A case report
(2019) Ozcan, Deren; Vural, Ayse Tuncer; Ozen, Ozlem; 0000-0002-7450-6886; 31443128
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-7232-2020
Object. 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.
A Rat Model of Acute Respiratory Distress Silymarin's Antiinflamatory and Antioxidant Effect
(2016) Adiguzel, Senay Canikli; Pirat, Arash; Turkoglu, Suna; Bayraktar, Nilufer; Ozen, Ozlem; Kaya, Muge
Objective: In this study, it was aimed to evaluate the anti-inflammatory and antioxidative effects of Silymarin in rats in whom artificial acute pulmonary damage was provided with caecal ligation-perforation method. Material and Method: Forty-six rats were randomized to sham (n=14), control (n=16), silymarin (n=16) groups. Each group had early and late subgroups. Silimarin was administered in the silimarin group and saline was administerd in control and sham groups. Artificial acute pulmonary damage associated with sepsis was provided with caecal ligation-perforation method in control and silimarin groups. Rats in the early subgroup Were terminated at the end of the 12th hour and threats in the late group were followed-up. Serum and bronchoalveolar lavage fluid (BAL) tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6; lung tissue malondialdehyde (MDA) and glutathione (GSH) levels; lung histopathologic examination; and lung wet-to-dry (w/d) weight ratio measurements were used to compare and evaluate the severity of lung injury between the groups. Results: Mortality rates for silymarin and control groups were 62.5% and 12.5%, respectively (log-rank p=0.0506). Compared with the silymarin group, the control group exhibited significantly more severe lung injury, as indicated by higher mean values for serum and BAL TNF-alpha, IL-1beta and IL-6 (p<0.05 for all measurements), total lung histopathologic injury score (p=0.001), w/d (p=0.019) and lung-tissue MDA (p=0.011) levels. Lung tissue GSH levels were significantly higher in silymarin group than control group (p=0.001). Conclusion: Silymarin reduces the severity of sepsis induced-acute lung injury and may also improve survival in a cecal ligation and perforation rat model. These beneficial effects of this agent are probably due to its inhibitory effects on inflammatory process and oxidative injury.
Recurrence patterns and prognostic factors in lymphovascular space invasion-positive endometrioid endometrial cancer surgically confined to the uterus
(2019) Sahin, Hanifi; Meydanli, Mehmet Mutlu; Sari, Mustafa Erkan; Kocaman, Eda; Cuylan, Zeliha Fırat; Yalcin, Ibrahim; Coban, Gonca; Ozen, Ozlem; Sirvan, Levent; Gungor, Tayfun; Ayhan, Ali; 30638487
Objective: The purpose of this study was to determine the patterns of failure and prognostic factors for lymphovascular space invasion (LVSI)-positive endometrioid endometrial cancer (EC) patients in the setting of negative lymph nodes (LNs). Materials and methods: A multicenter, retrospective department database review was performed to identify LVSI-positive patients with disease surgically confined to the uterus at two gynecologic oncology centers in Turkey. Demographic, clinicopathological and survival data were collected. Results: We identified 185 LVSI-positive women with negative LNs during the study period. Fifty-five (29.7%) were classified as Stage IA, 94 (50.8%) as Stage IB, and 36 (19.5%) as Stage II. The median age at diagnosis was 59 years and the median duration of follow-up was 44 months. The total number of the recurrences was 12 (6.5%). We observed 5 (2.9%) loco-regional recurrences, 3 (1.5%) retroperitoneal failures, and 4 (2.0%) distant relapses. The 5-year progression-free survival (PFS) was 86.1% while the 5-year overall survival (OS) rate was 87.7%. Grade 3 histology (Hazard Ratio [HR] 2.9, 95% Confidence Interval [CI] 1.02-8.50; p = 0.04), cervical stromal invasion (HR 4.5, 95% CI 1.61-12.79; p = 0.004) and age > 60 years (HR 5.8, 95% CI 1.62-21.32; p = 0.007) were found to be independent prognostic factors for decreased OS. Adjuvant treatment did not appear as a prognostic factor for OS even in univariate analysis. Conclusion: The recurrence rate among LVSI-positive endometrioid EC patients is low in the setting of negative LNs. However, one out of three patients with a recurrence experiences distant relapses which usually portend worse outcomes. (C) 2018 Taiwan Association of Obstetrics & Gynecology. Publishing services by Elsevier B.V.
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; 34856570
Endocervical 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.
Robust diagnosis of Ewing sarcoma by immunohistochemical detection of super-enhancer-driven EWSR1-ETS targets
(2018) Ozen, Ozlem; Baldauf, Michaela C.; Orth, Martin F.; Dallmayer, Marlene; Marchetto, Aruna; Gerke, Julia S.; Rubio, Rebeca Alba; Kiran, Merve M.; Musa, Julian; Knott, Maximilian M. L; Ohmura, Shunya; Li, Jing; Akpolat, Nusret; Akatli, Ayse N.; Dirksen, Uta; Hartmann, Wolfgang; de Alava, Enrique; Baumhoer, Daniel; Sannino, Giuseppina; Kirchner, Thomas; Gruenewald, Thomas G. P.; 0000-0002-9082-1317; 29416716; AAK-4468-2021
Ewing sarcoma is an undifferentiated small-round-cell sarcoma. Although molecular detection of pathognomonic EWSR1-ETS fusions such as EWSR1-FLI1 enables definitive diagnosis, substantial confusion can arise if molecular diagnostics are unavailable. Diagnosis based on the conventional immunohistochemical marker CD99 is unreliable due to its abundant expression in morphological mimics. To identify novel diagnostic immunohistochemical markers for Ewing sarcoma, we performed comparative expression analyses in 768 tumors representing 21 entities including Ewing-like sarcomas, which confirmed that CIC-DUX4-, BCOR-CCNB3-, EWSR1-NFATc2-, and EWSR1-ETS-translocated sarcomas are distinct entities, and revealed that ATP1A1, BCL11B, and GLG1 constitute specific markers for Ewing sarcoma. Their high expression was validated by immunohistochemistry and proved to depend on EWSR1-FLI1-binding to highly active proximal super-enhancers. Automated cut-off-finding and combination-testing in a tissue-microarray comprising 174 samples demonstrated that detection of high BCL11B and/or GLG1 expression is sufficient to reach 96% specificity for Ewing sarcoma. While 88% of tested Ewing-like sarcomas displayed strong CD99-immunoreactivity, none displayed combined strong BCL11B-and GLG1-immunoreactivity. Collectively, we show that ATP1A1, BCL11B, and GLG1 are EWSR1-FLI1 targets, of which BCL11B and GLG1 offer a fast, simple, and cost-efficient way to diagnose Ewing sarcoma by immunohistochemistry. These markers may significantly reduce the number of misdiagnosed patients, and thus improve patient care.
SEROUS VERSUS HIGH-GRADE ENDOMETRIOID ENDOMETRIAL CARCINOMA: IMMUNOHISTOCHEMISTRY OF RFP IS NOT USEFUL FOR DIFFERENTIATION
(2016) Ussakli, Cigdem; Usubutun, Alp; Dicner, Nazmiye; Dolgun, Anil; Bulbul, Dilek; Isikdogan, Zuhal; Haberal, Nihan; Ozen, Ozlem; Tezel, Gaye Guler; 0000-0001-9852-9911; 28155970; AAK-4587-2021
We evaluated the immunohistochemical expression of ret finger protein (RFP) along with conventional immunohistochemical markers in endometrioid and serous carcinomas of the endometrium. A total of 124 endometrial carcinoma cases (24 grade 1 endometrioid, 60 grade 3 endometrioid, 40 serous) were retrieved from pathology archives. Tissue microarrays were constructed. The expression of RFP, WT1, ER., PR, p53 and p16 was examined immunohistochemically. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve, kappa statistic for interobserver reproducibility, Kruskal-Wallis test, Mann-Whitney U test and Fisher's exact tests were performed for statistical analyses. The mean RFP score was 1.54 in grade 1 endometrioid, 4.31 in grade 3 endometrioid, and 6.31 in serous carcinomas (p < 0.001). Overall, RFP scores were higher both in serous and grade 3 endometrioid carcinoma (p > 0.05), and significantly lower in grade 1 endometrioid carcinoma (p < 0.05). p16 and p53 staining patterns were able to differentiate between high-grade endometrioid and serous carcinoma (p < 0.001). ER, PR and WT-1 did not reach statistical significance for subtyping. The kappa values of the general agreement between the observers were 0.737 and 0.727 for endometrioid and serous carcinomas respectively (p < 0.001). Diffuse p53 and p16 staining provides the most sensitive and specific immunomarkers for differentiating high-grade endometrioid and serous carcinomas.