Browsing by Author "Isisag A."
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Item Histopathological and immunohistochemical clues in the differential diagnosis of benign and malignant focal lymphocytic aggregates in paraffin sections of the bone marrow biopsies(1998) Isisag A.; Hekimgil M.; Soydan S.; Ayhan S.; Turkdogan P.One of the problems in evaluating bone marrow trephine biopsies is to determine whether a focal lymphocytic aggregate is benign or not. To assess the value of anti-bcl-2 monoclonal antibody on the differential diagnosis, bone marrow biopsies with focal lymphocytic aggregates were evaluated by conventional histopathological criteria and an immunohistochemical study using anti-bcl-2 monoclonal antibody was performed. Of the 27 bone marrow trephine biopsies from patients with lymphoproliferative disorders malignant aggregates were found in 14. The remaining 13 contained benign aggregates according to the conventional criteria and in none of these cases malignancy was confirmed. Conventional criteria were tested by comparing the histopatological characteristics of benign and malignant aggregates. The trephine biopsies of all 27 cases were immunostained with anti-bcl-2 antibody. A moderate to intense nuclear staining in the mononuclear calls of the aggregates was observed in 12 of 14 malignant cases. None of the cases diagnosed as benign stained with the anti-bcl-2 monoclonal antibody. It is concluded that positive immunostaining with this antibody strongly suggests that a focal lymphocytic aggregate is malignant.Item Reproducibility of the 1998 World Health Organization/International Society of Urologic Pathology classification of papillary urothelial neoplasms of the urinary bladder(2003) Yorukoglu K.; Tuna B.; Dikicioglu E.; Duzcan E.; Isisag A.; Sen S.; Mungan U.; Kirkali Z.Objectives: This study assessed the diagnostic agreement and intra- and inter-observer reproducibility of the World Health Organization/International Society of Urologic Pathology Consensus Classification of Urothelial Neoplasms (1998 WHO/ISUP classification) and the 1973 WHO classification. Methods: A teaching set with 5 slides of each papillary neoplasm of low malignant potential, low-grade papillary carcinoma, high-grade papillary carcinoma, and a guideline, as well as a study set of 30 slides containing ten cases of each category, were sent to participants. Six pathologists expert in urological pathology reviewed the 30 slides of non-invasive papillary urothelial tumors in the study set. Diagnostic accuracy and reproducibility were evaluated using intra- and inter-rater techniques (kappa statistic). Results: A moderate to substantial intra- and inter-observer reproducibility was achieved for both the 1998 WHO/ISUP and 1973 WHO classification. The results of the two classification systems were not different statistically (P>0.05). Reproducibility was lower in low-grade tumors for both classifications. Conclusions: The new proposed classification system for non-invasive urothelial neoplasms does not increase the reproducibility. There is still a need for uniformity in grading in order to compare the different studies and therapies and to provide more accurate information for management.Item Primary orbital neuroblastoma in a neonate(Medknow Publications and Media Pvt. Ltd, 2006) Mirzai H.; Baser E.; Tansug N.; Nese N.; Isisag A.Neuroblastoma is an undifferentiated malignant tumor of the primitive neuroblasts. Orbital neuroblastoma is typically a metastatic tumor. We describe a two-days-old girl, who presented with a large tumor in her left orbit. Magnetic resonance imaging revealed that the tumor originated from the retrobulbar area, extending into the upper and lateral orbit. She was operated on the fifth day of life. A histopathologic diagnosis of neuroblastoma was made. Medical evaluation including chest roentgenogram, ultrasonography of the abdomen, whole body computerized tomogram and bone scintigraphy showed no evidence of systemic involvement or metastasis. Neuroblastoma should be considered in the differential diagnosis of neonatal orbital tumors.Item Urachal urothelial carcinoma diagnosed at a radical prostatectomy operation: A case report(2010) Nese N.; Kesici G.; Lekili M.; Isisag A.BACKGROUND: Urachal carcinomas are rare tumors, and the majority of them are adenocarcinomas. Up to now, only 21 urachal urothelial carcinomas (UCas) have been reported. Here, we describe a case of high grade UCa arising from the urachal remnants. CASE: A 66-year-old man presented with voiding difficulties. Prostate specific antigen (PSA) was 5.46 ng/mL. Prostatic adenocarcinoma (PCa) (Gleason score 6) was diagnosed by needle biopsies. After the diagnosis of high grade, muscle invasive UCa with intact mucosa on frozen examination of the dome of bladder wall during the radical prostatectomy operation (RPO), partial cystectomy was performed. Microscopically, among the tumoral islands, cystic structures lined by cells with a benign appearance, which are considered urachal remnants, were noted. Cytokeratin 7 and high-molecular-weight cytokeratin were strongly positive, PSA and carcinoembryonic antigen were negative. Radiotherapy was given for both UCa and PCa. Six months after the diagnosis, an undifferentiated tumor was detected in a bladder transurethral resection specimen; thus, chemotherapy was given. After 1 course of chemotherapy, the patient was doing well. CONCLUSION: The origin of urachal carcinomas is usually obscured as it is a highly invasive carcinoma. The patient presented here was diagnosed incidentally during RPO. Although the stage was advanced, the tumor was detected before urachal remnants were destroyed. The treatment choice for urachal carcinomas is cystectomy. Adjuvant chemotherapy and radiotherapy are controversial. © Science Printers and Publishers, Inc.Item Immunohistochemical analysis of Ki-67, p53 and Bcl-2 expression related to histological features in gastroesophageal reflux disease(2010) Ayhan S.; Ak Nalbant O.; Isisag A.; Türkel Küçükmetin N.; Temiz P.Background/aims: The endoscopic and histologic findings of gastroesophageal reflux disease are usually indistinct. The current study was designed to define accurately the histology in gastroesophageal reflux disease and to develop a hypothesis that reflux produces immunohistochemical changes. Methods: The study was based on the examination of endoscopic esophageal biopsy specimens obtained from 20 patients with evidence of reflux with 24-hour pH-meter monitoring and from 20 control subjects without clinical or endoscopic reflux. The pathogenesis of reflux esophagitis was discussed by comparing the histopathologic changes with determined Ki-67, p53 and Bcl-2 immunoreactivity. Results: In this study, the presence of esophagitis was determined endoscopically in only 55% of the patients with gastroesophageal reflux disease, while microscopic esophagitis was detected in 60% of them. No correlation was found between presence of endoscopic esophagitis and microscopic esophagitis in the patients with gastroesophageal reflux disease. There was a significant difference between control cases and the patients according to histological parameters, which included basal activity (p=0.006), height of papillae (p=0.006), intraepithelial neutrophils (p=0.000), intraepithelial eosinophils (p=0.006), congestion (p=0.001), and dilated intercellular spaces (p=0.006). Immunohistochemically, there was a significant difference in the expression of p53 and Ki-67 between the three study groups (patients with/without microscopic esophagitis, controls) (p<0.05). However, there was no difference in Bcl-2 between the patients with reflux and control cases. Conclusions: In this study, we considered that microscopic esophagitis does not always accompany reflux, and the lack of reliable diagnostic histologic criteria is still a serious problem for pathologists. Immunohistochemically, an increase in cell proliferative activity and p53 protein accumulation to repair oxidative DNA damage related to reflux were observed. However, the close Bcl-2 immunoreactivity in all groups that was indicated by a weak positivity suggests that the inhibition of apoptosis may not be involved in reflux esophagitis.Item The role of pRB, p16 and cyclin D1 in colonic carcinogenesis(2010) Ayhan S.; Isisag A.; Saruc M.; Nese N.; Demir M.A.; Kucukmetin N.T.Background/ Aims: This study is aimed to investigate abnormal expression of the Rb protein (pRb), p16INK4a (p16) and cyclin D1 in colorectal adenomas and adenocarcinomas and to assess the possible alterations in Rb pathway in colorectal carcinogenesis. METHODOLOGY: 44 cases of colorectal adenoma and 44 cases of colorectal adenocarcinoma were examined histopathologically and immunohistochemically using monoclonal antibodies to identify abnormalities of pRb, p16, and cyclin D1 expression. Staining degree of above-mentioned markers was assessed by using a semi-quantitative method in all cases in order to determine any staining differences. RESULTS: In 70.5% of the adenomas and 97.7% of the adenocarcinomas, an overexpression of pRb was found. There was a statistically significant relationship between the immunoreactivity of pRb and villous/ tubulovillous types of adenomas (p<0.05). There was a loss of p16 expression in 84.1% of adenomas and 61.4% of adenocarcinomas. Statistically significantly, the p16 overexpression was not seen in any of tubular adenomas (p<0.001). Overexpression of cyclin D1 was found in only 9.1% of adenomas, while 31.8% of adenocarcinomas overexpressed this protein. Loss of expression of cyclin D1 was similar in adenomas and adenocarcinomas (27.3% and 25%, respectively). Staining degrees of all three cell cycle proteins were shown to be statistically different in adenomas and adenocarcinomas, for pRb (p=0.001), for p16 (p=0.045), and cyclin D1 (p=0.05). Also, there was only a mild agreement with respect to p16 and cyclin D1 relationship between for adenomas (K=+0,28 p=0,051) and for adenocarcinomas (K=+0,35 p=0,017). Besides, there was no correlation between the expression of pRb, p16, and cyclin D1 and clinicopathological tumor characteristics and prognostic data such as stage or lymph node/liver metastasis. CONCLUSIONS: pRb, p16 and cyclin D1 are shown to be aberrantly expressed in both colorectal adenomas and adenocarcinomas. It can be claimed that disturbances in Rb pathway take part in colonic carcinogenesis and pRb, p16 and cyclin D1 play an ever increasing role in the further stages of adenoma-carcinoma sequence. © H.G.E. Update Medical Publishing S.A.Item Does asthma control as assessed by the asthma control test reflect airway inflammation?(BioMed Central Ltd., 2011) Bora M.; Alpaydin A.O.; Yorgancioglu A.; Akkas G.; Isisag A.; Coskun A.S.; Celik P.Background and aims: The treatment of asthmatic patients is particularly focused on the control of symptoms as well as functional and inflammatory parameters. In our study, we investigated the relationship between the asthma control test (ACT) which evaluates symptoms and airway inflammation and functional parameters. Materials and methods: Stable asthmatic patients admitted to our pulmonary outpatient clinic were enrolled in the study consecutively and underwent the ACT, pulmonary function tests and methacholine bronchial provocation test (MBPT). Additionally, fractional exhaled nitric oxide level (FeNO) and induced sputum cell distribution were assessed. All these parameters were re-evaluated at the third month after adjusting medications of the patients according to baseline ACT scores. Results: Of the 101 patients screened, we analyzed 83 who proceeded to the follow up visit. At the baseline visit, 8 were totally controlled, 36 partially controlled and 39 uncontrolled according to ACT. At the follow up visit, 10 were totally controlled, 39 partially controlled and 34 uncontrolled. Comparison of the two visits in terms of all parameters revealed significant reductions only in the percentages of patients with MBPT positivity (p = 0.029) and FeNO levels > 20 ppb (p = 0.025) at follow up. The percentages of patients with FeNO > 20 ppb, MBPT positivity, induced sputum eosinophilia or induced sputum neutrophilia did not show significant differences between totally controlled, partially controlled and uncontrolled groups at both baseline and follow up visits. Conclusion: Although the ACT scores did not show significant correlations with the airway inflammation parameters tested in this study, a marked reduction in the percentage of patients with MBPT positivity and FeNO > 20 ppb at follow up may suggest the importance of the control concept in the management of asthma.Item Square IgM crystals in bone marrow in Waldenström macroglobulinaemia(Blackwell Publishing Ltd, 2016) Erdem N.; Ulu I.; Miskioglu H.M.; Isisag A.; Aydogdu I.[No abstract available]Item Sonic hedgehog, TBX18, and TSHZ3 proteins involved in pyeloureteral motility development are overexpressed in ureteropelvic junction obstruction: An immunohistochemical, histopathological, and clinical comparative study(Saudi Arabian Armed Forces Hospital, 2016) Yilmaz O.; Nese N.; Dalgic M.; Kesici G.P.; Genc A.; Taneli C.; Gunsar C.; Sencan A.; Cayirli H.; Isisag A.Objectives: To compare pathological samples obtained from cases that underwent surgery for ureteropelvic junction (UPJ) obstruction with samples obtained during autopsies of subjects. Methods: Retrospectively, 42 patients who had undergone surgery due to UPJ obstruction (group 1) were included in the study. Histopathological and immunohistochemical features for sonic hedgehog (SHH), TBX18, and TSHZ3 of UPJ were evaluated and findings were compared with 20 autopsy cases (group 2). Original Articles Results: In group 1, the scores were statistically significantly higher in terms of cytoplasmic SHH, nuclear TBX18, cytoplasmic and nuclear TSHZ3 staining. Statistically, no correlation was found between age and the staining scores belonging to these 3 antibodies in group 1 and group 2. Intense inflammation was found to be related with nuclear staining for TBX18. Conclusion: Gene product expressions of SHH, TBX18 and TSHZ3 are statistically higher in patients with UPJ obstruction, when compared with control group. The explanation may be the reactivation of the processes, which had shown their effects in the embryological period, due to the chronic inflammation and long-term micro-trauma created by the disease. © 2016, Saudi Arabian Armed Forces Hospital. All rights reserved.Item Predictive value of cyclooxygenase-2 over expression for identifying prostate cancer from benign prostatic hyperplasia in prostate biopsy specimens(Edizioni Minerva Medica, 2016) Ceylan Y.; Lekili M.; Muezzinoglu T.; Nese N.; Isisag A.BACKGROUND: We studied cyclooxygenase-2 (COX-2) immunohistochemical staining intensity both in prostatic biopsy and surgical samples of patients with prostate cancer to determine if it might provide prognostic information for the decision of re-biopsy indication. METHODS: Twenty-eight patients undergone radical prostatectomy whose final pathologic examination revealed prostatic adenocarcinoma were included in the study. Twelve patients with BPH in their pathological examination of both prostatic biopsy and open prostatectomy were considered as a control group. Intensity of COX-2 receptor was examined with immunohistochemical staining according to standard techniques. RESULTS: Positive COX-2 receptor staining was obtained 89.3% of biopsy samples and 93% of surgical samples in all cancer patients. The rate of agreement in COX-2 receptor staining of biopsy samples and radical prostatectomy samples was 76% in same patients (P=0.54). Similarly, the COX-2 receptor levels in biopsy specimens of patients with BPH open surgery compared with samples of the agreement still rate was 41% (P=0.41). Prostate cancer exchanging COX-2 receptor levels in patients with biopsy specimens in patients with BPH were found significantly more (P=0.008). CONCLUSIONS: In this study the feasibility of presence of COX-2 receptor staining in biopsy samples was shown. We have also demonstrated that COX-2 staining intensity was higher in prostatic biopsy samples of patients with prostatic cancer than patients with BPH. This leads a conclusion that, higher COX-2 expression levels in biopsy specimens may be used to decide re-biopsy in borderline preoperative PSA levels as well as in the cases with suspicious pathological findings for cancer. © 2014 EDIZIONI MINERVA MEDICA.Item Relationship of tumor-associated macrophage population detected by CD68 pg-m1, CD68 kp1, and cd163 with latent ebv infection and prognosis in classical hodgkin lymphoma(Federation of Turkish Pathology Societies, 2021) Mavili H.S.; Isisag A.; Tan A.; Miskioglu M.; Saka Baraz L.; Nese N.Objective: To evaluate the quantity of tumor-associated macrophages (TAMs) in cases of Hodgkin Lymphoma of classical type (cHL), and to reveal possible associations between TAM intensity and latent Epstein-Barr virus (EBV) infection, overall survival, progression-free survival, prognostic indices, and clinicopathological parameters. Materials and Methods: A total 46 cases of cHL with complete clinical records were selected and re-evaluated histopathologically. Staining for CD68 (PG-M1; KP1 clones) and CD163 was evaluated and the cut-off values were defined. Also, all cases were evaluated using the chromogen in situ hybridization (CISH) method with EBER (Epstein-Barr virus-encoded RNA) probes for the presence of possible EBV infection. Results: It was found that high expression levels of PG-M1 and high International Prognostic Scores (IPS) were associated with shortened overall survival (p=0.047, p=0.013). Cases with 2 or less areas of nodal region involvement were observed to have longer progression-free survival period (p=0.043). Higher expression levels of CD68 PG-M1, CD68 KP1, and CD163 were found to show significant associations with the presence of some clinical parameters such as the presence of B symptoms, spleen involvement, and the presence of EBV infection. Conclusions: Our findings suggest that increase of PG-M1+ TAM is associated with shortened overall survival, while higher expressions of all immunohistochemical markers are statistically significantly associated with the presence of EBV infection and clinical parameters mentioned above. These findings indicate that highlighting the TAM rate via macrophage markers in cases of cHL could be helpful in determining the prognostic risk groups and the relevant results should be mentioned in pathology reports. © 2021, Federation of Turkish Pathology Societies. All rights reserved.Item C-MET positivity and its relationship with histopathological findings in gastric carcinomas exhibiting HER2 gene expression(Wolters Kluwer Medknow Publications, 2022) Coskun F.; Ayhan S.; Tan A.; Isisag A.Context: Co-expressions of receptor tyrosine kinases such as c-MET and HER2 were reported in many studies. The concomitant expression is associated with more aggressive clinical course. Aims: In this study, it was intended to investigate the correlation of the positivity of c-MET and HER2 with histopathologic findings and their impacts on prognosis. Subjects and Methods: After the decision of the ethics committee, a total of 64 cases, whose HER 2 status was studied by dual silver in situ hybridization/immunohistochemistry method, were included in the study. Immunohistochemical staining for c-MET was performed to all cases and the evaluation was performed similarly to the criteria for HER2 evaluation, but cytoplasmic staining was also considered significant. Statistical Analysis Used: The data were analyzed using SPSS 20 for Windows. Results: c-MET positivity which is considered by the score of 2+ and 3+ was found only in 34.4% of HER2 positive cases while it was 59.3% in HER2 negative cases (P = 0.045). The sole histopathological feature associated with c-MET positivity was distal gastric localization (P = 0.016). Conclusions: Even though higher rates of c-MET positivity in HER2 positive cases were stated in the literature, contrary results were obtained in this study. Comparing the HER2+/c-MET + co-expression group with the other groups, no difference was found about age, sex, macroscopic and microscopic characteristics. The presence of c-MET positivity in cases with HER2 expression suggests that c-MET expression might be associated with the resistance to Trastuzumab. © 2022 Chinese Journal of Physiology.