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Item High Specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG Positive Ewing Sarcoma(2020) Oezen, Oezlem; 0000-0002-9082-1317; 32164354; AAK-4468-2021Ewing sarcoma (EwS) is an aggressive cancer displaying an undifferentiated small-round-cell histomorphology that can be easily confused with a broad spectrum of differential diagnoses. Using comparative transcriptomics and immunohistochemistry (IHC), we previously identified BCL11B and GLG1 as potential specific auxiliary IHC markers for EWSR1-FLI1-positive EwS. Herein, we aimed at validating the specificity of both markers in a far larger and independent cohort of EwS (including EWSR1-ERG-positive cases) and differential diagnoses. Furthermore, we evaluated their intra-tumoral expression heterogeneity. Thus, we stained tissue microarrays from 133 molecularly confirmed EwS cases and 320 samples from morphological mimics, as well as a series of patient-derived xenograft (PDX) models for BCL11B, GLG1, and CD99, and systematically assessed the immunoreactivity and optimal cut-offs for each marker. These analyses demonstrated that high BCL11B and/or GLG1 immunoreactivity in CD99-positive cases had a specificity of 97.5% and an accuracy of 87.4% for diagnosing EwS solely by IHC, and that the markers were expressed by EWSR1-ERG-positive EwS. Only little intra-tumoral heterogeneity in immunoreactivity was observed for differential diagnoses. These results indicate that BCL11B and GLG1 may help as specific auxiliary IHC markers in diagnosing EwS in conjunction with CD99, especially if confirmatory molecular diagnostics are not available.Item Prostaglandin F receptor expression in intrauterine tissues of pregnant rats(2014) Anadol, Elvan; Kanca, Halit; Yar, Atiye Seda; Helvacioglu, Fatma; Menevse, Sevda; Calguner, Engin; Erdogan, DenizIn this investigation, we studied the expression and localization of rat prostaglandin F (FP) receptor in uterine tissues of rats on gestational Days 10, 15, 18, 20, 21, 21.5 and postpartal Days 1 and 3 using Western blotting analysis, real-time PCR, and immunohistochemistry. A high level of immunoreactivity was observed on gestational Days 20, 21, and 21.5 with the most significant signals found on Day 20. FP receptor protein was expressed starting on gestational Day 15, and a fluctuating unsteady increase was observed until delivery. Uterine FP receptor mRNA levels were low between Days 10 and 18 of gestation (p < 0.05). The transcript level increased significantly on Day 20 and peaked on Day 21.5 just before labor (p < 0.05). There was a positive correlation between FP receptor mRNA expression and serum estradiol levels (rs = 0.78; p < 0.01) along with serum estradiol/progesterone ratios (rs = 0.79; p < 0.01). In summary, we observed an increase FP receptor expression in rat uterus with advancing gestation, a marked elevation of expression at term, and a concominant decrease during the postpartum period. These findings indicate a role for uterine FP receptors in the mediation of uterine contractility at term.Item Association of metallothionein expression and clinical response to cisplatin based chemotherapy in testicular germ cell tumors(2015) Tuzel, Emre; Yorukoglu, Kutsal; Ozkara, Esra; Kirkli, Ziya; 25914837Introduction The protective roles of metallothioneins (MT) against metal toxicity suggest that MT may have a functional role in cisplatin resistance. The aim of this study was to investigate the expression of MT in specimens of germ cell tumors and compare it with clinical sensitivity to cisplatin based chemotherapy. Material and methods Tissue blocks of primary GCT specimens obtained from 39 patients were examined immunohistochemically for MT expression. Staining intensity was evaluated according to the percentage of MT positive cells and graded as [-], [+] and [++]. The staining characteristics were compared with the clinical response to chemotherapy. Results Of the 39 tumors, 3 evidenced no MT expression while 26 and 10 specimens showed [+] and [++] staining, respectively. Although seminomas tend to stain weaker than non-seminomas, the difference of staining between them was not significant (p = 0.19). Of the 39 patients, 23 underwent cisplatin based chemotherapy. Of those, 6 progressed and 17 achieved complete remission. Of the non-responders, 5 showed [+] and 1 showed [++] staining. Six of the responders showed [+], 10 had [++] and 1 showed no staining. No association was found between MT staining and chemo-sensitivity (p = 0.53). Conclusions MT expression in primary germ cell tumors did not differ between responding and non-responding patients and therefore may not be useful in predicting response to chemotherapy.