Wos Açık Erişimli Yayınlar

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2016 - 20182

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Author: search.filters.author.Ozen, OzlemSubject: search.filters.subject.Immunohistochemistry

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    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.
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    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.