Wos Açık Erişimli Yayınlar
Permanent URI for this collectionhttps://hdl.handle.net/11727/10754
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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 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; 30638487Objective: 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.Item Uterine smooth muscle tumor of uncertain malignant potential: fertility and clinical outcomes(2019) Sahin, Hanifi; Karatas, Funda; Coban, Gonca; Ozen, Ozlem; Erdem, Ozlem; Onan, Mehmet Anil; Ayhan, Ali; 0000-0002-3285-5519; 31074239Objective: In this study, we aimed to evaluate the clinicopathological features, obstetric, and oncological outcomes of patients diagnosed with a uterine smooth muscle tumors of uncertain malignant potential (STUMP). Methods: A dual-institutional, database review was carried out to screen patients with STUMP who were treated with upfront surgery between January 2006 and December 2017. Data including age at the time of diagnosis, recurrence rate, disease-free survival, overall survival, and fertility outcomes were retrospectively analyzed. Results: Fifty-seven patients with STUMPs were included in the study. The median age at the time of diagnosis was 42 (range, 16 to 75) years. The median follow-up was 57 (range, 16 to 125) months. Eight patients (14%) had recurrence during follow-up. Recurrent STUMPs were seen in seven patients and leiomyosarcoma after 14 months in one patient. Seven patients with a recurrent STUMP survived, while the remaining patient died. Recurrence rates were similar for women who underwent myomectomy and those who underwent hysterectomy. The presence of uterine localization of tumor (subserosal vs intramural-submucosal) statistically significantly affected recurrence rates (odds ratio=5.72; 95% confidence interval=1.349-24.290; p=0.018). Ten of 27 patients who underwent myomectomy for uterine myoma had fertility desire. Seven pregnancies were recorded. Conclusions: Our study results suggest that fertility-sparing approaches are feasible in patients with STUMP, although recurrence may be seen.Item Microsatellite Instability in Glioblastoma: Is It Really Relevant in Tumor Prognosis?(2019) Tepeoglu, Merih; Borcek, Pelin; Ozen, Ozlem; Altinors, Nur; 31529454AIM: 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.Item 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, AliBackground: 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.Item 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; 27262706Background: 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.Item 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-4587-2021We 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.Item 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-4468-2021Ewing 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.Item Systematic identification of cancer-specific MHC-binding peptides with RAVEN(2018) Ozen, Ozlem; Baldauf, Michaela C.; Gerke, Julia S.; Kirschner, Andreas; Blaeschke, Franziska; Effenberger, Manuel; Schober, Kilian; Rubio, Rebeca Alba; Kanaseki, Takayuki; Kiran, Merve M.; Dallmayer, Marlene; Musa, Julian; Akpolat, Nurset; Akatli, Ayse N.; Rosman, Fernando C.; Sugita, Shintaro; Hasegawa, Tadashi; Sugimura, Haruhiko; Baumhoer, Daniel; Knott, Maximilian M. L.; Sannino, Giuseppina; Marchetto, Aruna; Li, Jing; Busch, Dirk H.; Feuchtinger, Tobias; Ohmura, Shunya; Orth, Martin F.; Thiel, Uwe; Kirchner, Thomas; Gruenewald, Thomas G. P.; 30228952Immunotherapy can revolutionize anti-cancer therapy if specific targets are available. Immunogenic peptides encoded by cancer-specific genes (CSGs) may enable targeted immunotherapy, even of oligo-mutated cancers, which lack neo-antigens generated by protein-coding missense mutations. Here, we describe an algorithm and user-friendly software named RAVEN (Rich Analysis of Variable gene Expressions in Numerous tissues) that automatizes the systematic and fast identification of CSG-encoded peptides highly affine to Major Histocompatibility Complexes (MHC) starting from transcriptome data. We applied RAVEN to a dataset assembled from 2,678 simultaneously normalized gene expression microarrays comprising 50 tumor entities, with a focus on oligo-mutated pediatric cancers, and 71 normal tissue types. RAVEN performed a transcriptome-wide scan in each cancer entity for gender-specific CSGs, and identified several established CSGs, but also many novel candidates potentially suitable for targeting multiple cancer types. The specific expression of the most promising CSGs was validated in cancer cell lines and in a comprehensive tissue-microarray. Subsequently, RAVEN identified likely immunogenic CSG-encoded peptides by predicting their affinity to MHCs and excluded sequence identity to abundantly expressed proteins by interrogating the UniProt protein-database. The predicted affinity of selected peptides was validated in T2-cell peptide-binding assays in which many showed binding-kinetics like a very immunogenic influenza control peptide. Collectively, we provide an exquisitely curated catalogue of cancer-specific and highly MHC-affine peptides across 50 cancer types, and a freely available software (https://github.com/JSGerke/RAVENsoftware) to easily apply our algorithm to any gene expression dataset. We anticipate that our peptide libraries and software constitute a rich resource to advance anti-cancer immunotherapy.Item 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; 28272666Primary 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.