Browsing by Author "Sayhan, S"

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    Immunolocalization of integrins and fibronectin in tubal pregnancy
    Inan, S; Giray, G; Vatansever, HS; Ozbilgin, K; Kuscu, NK; Sayhan, S
    Integrins are a large family of cell adhesion molecules that serve as receptors involved in cell-to-cell and cell-to-matrix interactions during implantation. We studied immunohistochemical staining of integrins (alpha3, alphaV, beta1, and alpha2beta1) and fibronectin in ectopic tubal pregnancy. Thirty fallopian tube samples with ectopic pregnancies and five normal tubal segments were obtained during ligation operations; the tatter specimens served as controls in the study. Formalin-fixed paraffin-embedded tissue sections were stained with hematoxylin-eosin or primary antibodies against alpha3, beta1, alphaV, and alpha2beta1 integrins and fibronectin, using the avidin-biotin-peroxidase method. A semi-quantitative grading system was used to compare staining intensities. In the control samples, immunostaining of all integrins was found in a single layer of tall columnar epithelial. cells, the lamina propria (Lp) and the muscular layer. Fibronectin staining was detected in the Lp and the muscular layer. Staining intensities of alpha3 and beta1 integrins and fibronectin were increased in the normal part of fallopian tubes with ectopic pregnancies. Staining of beta1 integrin was more intense than staining of beta3 and fibronectin, whereas there was no difference in alphaV and alpha2beta1 integrin expression between normal tubal tissue in the ectopic pregnancy group and control tubal tissue. In the tubal. pregnancy group at the site of implantation, staining intensity of alpha3 and beta1 integrins and fibronectin was strong in decidual cells, supporting tissue and placental villi, whereas alphaV and alpha2beta1 staining was mild. We concluded that integrins, especially beta1 and alpha3, and fibronectin may play a rote in progression of tubal implantation. Although the role of integrins has not yet been clearly defined, these molecules may function as markers of normal and abnormal states of receptivity. We like to suggest that integrins and fibronectin, which are needed in utero implantation, are expressed in tubal tissues during ectopic pregnancy and are involved in ectopic implantation. (C) 2004 Elsevier GmbH. All rights reserved.
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    The distributions of apoptosis and related proteins in ovarian endometriosis
    Vatansever, HS; Inan, S; Giray, G; Sayhan, S; Ozbilgin, K; Sanci, M
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    Significance of apoptosis related proteins on malignant transformation of ovarian tumors: A comparison between Bcl-2/Bax ratio and p53 immunoreactivity
    Zeren, T; Inan, S; Vatansever, HS; Sayhan, S
    In this study, we compared the immunoreactivities of Bcl-2, Bax and p53 proteins in ovarian tumors and related the immunohistochemical findings to the histological type of the tumors. Formalin-fixed, paraffin wax-embedded tissue sections from 40 patients who had serous-mucinous borderline tumors and serous-mucinous adenocarcinoma of the ovary (n = 10 each) were stained with hematoxylin-eosin (H&E). After histopathological examination, serial sections were stained immunohistochemically with primary antibodies to Bcl-2, Bax and p53 using an avidin-biotin-peroxidase method. A semi-quantitative grading system was used to compare the immunohistochemical staining intensities. The nuclear DNA fragmentation of apoptosis was determined using TUNEL method. As a result of immunohistochemical staining, increased immunoreactivity of Bcl-2 was observed in adenocarcinomas when compared to borderline tumors (P < 0.001). Strong immunoreactivity of Bcl-2 and mild immunoreactivities of Bax and p53 were detected in ovarian adenocarcinomas. There were no significant statistical differences in the immunoreactivity of Bax among the histological type of ovarian tumors. Whereas a balance was observed between the immunoreactivities of Bcl-2 and Bax in the borderline cases, and this balance was strongly changed toward the anti-apoptotic Bcl-2 protein in patients with adenocarcinoma. TUNEL staining of 'sections indicated apoptotic cells in the serous borderline tumors were about 8-fold higher than in the serous adenocarcinoma. The results of this study on apoptosis-related factors might help to develop novel protective and therapeutic approaches, such as isofiavonoids and isothiocyanates, which were associated with decreased Bcl-2/Bax ratio, against the malignant epithelial ovarian tumors. (C) 2014 Elsevier GmbH. All rights reserved.
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    Increased vascular surface density in ovarian endometriosis
    Inan, S; Kuscu, NK; Vatansever, S; Ozbilgin, K; Koyuncu, F; Sayhan, S
    Our goal in this study was to investigate the presence of atigiogenesis-related factors in endometriomas by evaluating their vascular surface densities. Thirty ovarian samples were included in the study. Of these, ten were histologically confirmed endometriomas, ten were ovarian specimens in the follicular phase and ten were ovarian specimens in the luteal phase, serving as controls. Histological specimens were immunostained for von Willebrand factor (vWF: factor VIII-related antigen) and CD34. The area with the highest microvessel density in endometriosis and in the normal ovary was evaluated by using an intercept grid. All microvessels in a specific field (X 100 magnification) were counted and vascular surface density was measured, as 164.01 +/- 21.26 vs. 125.15 +/- 11.28 and 117.44 +/- 9.27 by using vWF, and as 172.97 +/- 25.64 vs. 138.65 +/- 32.21 and 120.34 +/- 18.40 by using CD34 in endometriotic, follicular and luteal ovarian samples, respectively (p < 0.001). The mean vascular surface density was significantly higher in endometriosis than in the ovarian samples of the follicular phase or the luteal phase. No significant difference was seen between normal ovarian samples. Endometriosis was associated with angiogenic properties. Having demonstrated elevated angiogenic factors in endometriotic samples, we concluded that activation of angiogenesis might be a key factor in the pathogenesis of endometriosis.
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    Significance of tyrosine kinase activity on malign transformation of ovarian tumors
    Zeren, T; Inan, S; Vatansever, HS; Ekerbicer, N; Sayhan, S
    Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) are members of the polypeptide growth factor family. The epidermal growth factor-receptor (EGF-R) is a receptor tyrosine kinase of the ErbB family. Many types of cancer, including ovarian cancer, display enhanced EGF-R immunoreactivity on their cell surface membranes. Also, an increase in TGF-alpha synthesis and secretion usually occurs in human carcinoma cell lines. In this study, we compared the immunoreactivities of TGF-alpha and EGF-R in ovarian tumors and related immunohistochemical findings to the histological type of the tumors. Formalin-fixed, paraffin wax-embedded tissue sections from 40 patients who had serous-mucinous borderline tumor and serous-mucinous adenocarcinoma of the ovary (n = 10 each) were stained with hematoxylin-eosin and labeled for binding of primary antibodies against TGF-alpha and EGF-R using an avidin-biotin-peroxidase method. A semi-quantitative grading system was used to compare immunohistochemical labeling intensities. Increased immunoreactivity of EGF-R and moderate immunoreactivity of TGF-alpha was detected in adenocarcinomas. There was no significant difference in the immunoreactivity of TGF-alpha among the histologic types of ovarian tumors. The results of this study support the hypothesis that EGF-R may be a more useful marker than TGF-alpha in epithelial ovarian tumors. (c) 2007 Elsevier GmbH. All. rights reserved.
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    TGF-βs and SMADs Activities at the Site of Failed Neural Tube in the Human Embryos
    Barutcuoglu, M; Umur, AS; Vatansever, HS; Umur, N; Ozbilgin, K; Sayhan, S; Selcuki, M
    AIM: Transforming growth factor beta (TGF-beta) and Smads control intracellular signaling pathways in neurulation. Although previously reported similar experimental animal studies, the aim of this human study is to investigate the expression of TGF-beta (1,2,3) and Smads (1,2,3,6,7) in aborted human fetuses with myeloschisis. MATERIAL and METHODS: Twelve human fetuses with neural tube defect were obtained. They were stained with antibodies against TGF-beta 1, TGF-beta 2,TGF-beta 3, Smad (1,2,3), Smad 6 and Smad 7 using the indirect immunohistochemical technique. RESULTS: We noted mild immune reactivity of TGF-beta 1 and TGF-beta 2 in the open neural plate, motor neurons and surrounding tissue. Strong immune reactivity of TGF-beta 3 was shown in only open neural plate and surrounding tissue. Immunoreactivity of all Smads noted negative except Smad7. CONCLUSION: These results suggested at the site where the neural tube failed to close, TGF-beta 1,2 and Smads 1,2,3,6 do not continue their activity and decrease with internal timing of embryonic development. Additionally ectodermal layers are considered by embryo asnot closed wound and TGF-beta 3 activity may be an effort to repair the failed closure.
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    Immunolocalization of ERK1/2 and p-AKT in normal endometrium, endometrial hyperplasia, and early and advanced stage endometrioid endometrial adenocancer and their prognostic significance in malignant group
    Gungorduk, K; Ertas, IE; Sahbaz, A; Ozvural, S; Sarica, Y; Ozdemir, A; Sayhan, S; Gokcu, M; Yilmaz, B; Sanci, M; Inan, S; Harma, M; Yildirim, Y
    Objective: To analyze the expression patterns of extracellular signal-regulated kinase (ERK1/2) and phosphorylated (p)-AKT in the tissues of non-pathologic endometrium, endometrial hyperplasia, and early and advanced stage endometrioid endometrial adenocancer using indirect immunohistochemistry, and also to investigate the effect of ERK1/2 and p-ART expression patterns on prognosis in endometrioid adenocancer. Study design: Immunolocalization of ERK1/2 and p-Ala was examined in six different types of endometrial tissues: proliferative endometrium (PE; n = 10, 11.2%), secretuar endometrium (SE; n = 10, 11.2%), simple hyperplasia (SH; n = 15,16.9%), complex hyperplasia (CH; n=3, 3.4%) and atypical complex hyperplasia (ACH; n = 10, 11.2%), which were obtained from endometrial biopsies, curettage materials, and hysterectomy specimens and classified as the benign group; and both early stage endometrioid (n = 21, 23.6%) and advanced stage endometrioid adenocancer (AC; n=20, 22.5%), which were obtained from complete surgical staging materials and classified as the malignant group. All specimens were fixed in 10% formalin and processed using routine paraffin protocols. Immunostaining intensities were evaluated as negative or weak (assigned as low expression) and moderate or strong (assigned as high expression). Results: In the malignant group, 23 of 41 patients (56.1%) had high ERK1/2 and p-AKT expression, whereas only three of 48 patients in the benign group (6.3%) had high ERK1/2 and p-ART expression (P < 0.0001 and P < 0.0001, respectively), p-ART expression was significantly higher in women with positive lymph nodes (OR 9.0; 95% CI: 1.2-100.0; P = 0.03). Higher expression of p-Ala was significantly associated with poor progression-free survival (PFS) and overall survival (OS). In contrast, ERK1/2 expression was not associated with PFS or OS. Conclusions ERK1/2 and p-ART can be useful in the differential diagnosis of benign vs. malignant endometrial lesions, as well as early vs. advanced stage endometrioid endometrial adenocancer. Additionally, higher p-ART expression could be used as a marker of poor prognosis in the management of patients with endometrioid endometrial adenocancer. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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    Neural tissue continues its maturation at the site of neural tube closure defects
    Selçuki, M; Vatansever, S; Inan, S; Sanci, M; Sayhan, S; Bagdatoglu, C
    Objective. Our objective was to investigate the relation between the embryological development and neural tissue maturation at the site where the neural plate failed to form a neural tube. Material and methods. Samples from 15 aborted human fetuses with neural tube defects (NTD). All of the fetuses were between 20 and 25 gestational weeks old. Indicators of neural tissue maturation, formation of basal lamina, expression of integrins and neuron specific class III beta tubulin (tuj1) were investigated. To detect the adverse effects of the environment, if any, p53 and bcl-2 activity at both sites of the open and closed neural plate were investigated as well. Results. No difference was found in the expression of maturation-related molecules at the site of the neural plate that remained open compared with the site where the neural tube is normally formed. While high p53 activity was noted in neural tissue at the site of the neural tube defect, no such activity was detected in the neural tissue where the neural tube is normally formed. Conclusion. Our results suggested that maturation and differentiation of neural tissue continued regardless of the failure of neural tube closure. Therefore, the neurological deficits that are encountered in NTD patients should be related to secondary damage such as amnion fluid toxicity, uterus contractions, labor, etc. It seems valuable to save the neural plate before the negative effects of the environment renders the neural tissue functionless.
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    Synchronous primary endometrial and ovarian cancers: a multicenter review of 63 cases
    Solmaz, U; Karatasli, V; Mat, E; Dereli, L; Hasdemir, PS; Ekin, A; Gezer, C; Sayhan, S; Sanci, M; Guvenal, T
    Aims: To investigate clinicopathologic characteristics, therapeutic methods, and prognostic factors in women with synchronous primary endometrial and ovarian cancers (SEOCs). Methods: A retrospective review of 2 cancer registry databases in Turkey was conducted to identify patients diagnosed with SEOCs between January 1995 and December 2012. Patients with recurrent, metastatic, and metachronously occurring tumors were excluded. Multivariate logistic regression models were used to identify prognostic predictors for progression-free survival (PFS) and overall survival (OS). Results: The analysis included 63 women with SEOCs. Seventy-six percent of the patients had stage I endometrial cancer, and 60% of the patients had stage I ovarian cancer. Thirty-seven patients (58.7%) had endometrioid/endometrioid histology. Optimal cytoreduction was obtained in 47 (74.6%) patients. Recurrence developed in 17 patients (27%). Multivariate analysis confirmed lymphovascular space invasion (LVSI) as an independent poor prognostic factor for OS (odds ratio [OR] 3.1, p = 0.045), whereas early-stage disease and optimal cytoreduction were found to be independent good prognostic factors for both PFS (OR 12.85, p<0.001 and OR 4.58, p = 0.004, respectively) and OS (OR 7.31, p = 0.002 and OR 2.95, p = 0.028, respectively). The 3- and 5-year OS rates were 74% and 69%, respectively. Conclusions: Our study demonstrated that optimal cytoreduction, early-stage disease, and LVSI are the most significant factors affecting survival in women with SEOC.
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    Histologic grading of urothelial papillary neoplasms: impact of combined grading (two-numbered grading system) on reproducibility
    Tuna, B; Yörükoglu, K; Düzcan, E; Sen, S; Nese, N; Sarsik, B; Akder, A; Sayhan, S; Mungan, U; Kirkali, Z
    The clinical management of tumor patients is often strongly infuenced by the tumor grade. The presence of heterogeneity is well recognized in a variety of tumors. Overall grade is based on highest grade area identified within a tumor. Urothelial carcinoma often contains different histological grades within the same tumor. This study investigates the impact of a combined grading system on the reproducibility of papillary urothelial neoplasms. A set prepared for an earlier study consisting of ten cases of each category (papillary urothelial neoplasm of low malignant potential (PUNLMP), LGPUC, and HGPUC) was used. Agreement between pairs of pathologists was evaluated using kappa statistics for the combined scoring system. Interobserver agreement was fair to substantial as reflected by kappa values ranging from 0.24 to 0.74 (mean kappa = 0.43). The combined scores of 2 and 3 which included PUNLMP showed the lowest degree of agreement and when this category was excluded from the analysis, interobserver agreement increased significantly (mean kappa = 0.65; ranging from 0.43 to 0.92) in terms of combined scores of 4, 5, and 6. PUNLMP has been shown to be the least reproducible component of a combined scoring system even among experienced observers. Exclusion of PUNLMP from grading scheme seems to improve interobserver variability.
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    The distribution of apoptosis and related proteins in ovarian endometriosis
    Vatansever, SH; Inan, SV; Giray, GS; Sayhan, S; Ozbilgin, KM; Sanci, M