Burak Bahadir

Universal Markers of Thyroid Malignancies: Galectin-3, HBME-1, and Cytokeratin-19

Difficulties in diagnosis of thyroid lesions, even with histologic analysis, are well known. This study has been carried on to evaluate the role of immunohistochemical markers including galectin-3, Hector Battifora mesothelial cell-1 (HBME-1), and cytokeratin-19 in the diagnosis and differential diagnosis of benign and malignant thyroid lesions. The expressions of galectin-3, HBME-1, and cytokeratin-19 were tested in formalin-fixed, paraffin-embedded tissues from 458 surgically resected thyroid lesions including non-neoplastic and neoplastic lesions. Immunostaining with standard avidin–biotin complex technique was performed by using monoclonal antibodies. In malignant neoplastic thyroid lesions, galectin-3, HBME-1, and cytokeratin-19 were diffusely expressed in general. Diffuse expression rates of these three markers were 72.3% (47/65), 70.7% (46/65), and 76.9% (50/65), respectively. The use of galectin-3, HBME-1, and cytokeratin-19 may provide significant contributions in the differential diagnosis of malignant thyroid tumors. Although focal galectin-3, HBME-1, and cytokeratin-19 expression may be encountered in benign lesions, diffuse positive reactions for these three markers are characteristic of malignant lesions. It has concluded that cytokeratin-19 alone and its combinations with other markers were more sensitive in accurate diagnosis of papillary carcinoma than the other combinations; meanwhile, there were similar results for follicular carcinomas with HBME-1 alone and its combinations.

Clinicopathological significance of fascin and CD44v6 expression in endometrioid carcinoma

BackgroundFascin and CD44v6 may have significant roles as biomarkers in tumour progression and metastasis. In endometrioid carcinomas, the fascin expression profile is less defined, and the significance of CD44v6 is uncertain. We aimed to investigate the expressions of both fascin and CD44v6 in endometrioid carcinomas and to evaluate their inter-relation with clinicopathological parameters.MethodsFascin and CD44v6 expressions were evaluated, individually and in combination, in a series of 47 endometrioid carcinomas and 10 proliferative endometrium samples. The staining extent and intensity of both markers in tumour cells were scored semiquantitatively. The relationship between immunoexpressions and clinicopathological variables was assessed.ResultsThe expression rates of fascin and CD44v6 in endometrioid carcinoma were 72.34% and 46.80%, respectively. Although these expression rates were higher than those in proliferative endometrial samples, fascin expression showed a statistically significant difference from the normal group (p = 0.02), but CD44v6 did not differ (p = 0.54). Fascin expression was significantly correlated with tumour grade (p = 0.003) and neural invasion (p = 0.036) in a univariate analysis. In contrast, no significant correlation was found between CD44v6 and any of the clinicopathological parameters.ConclusionsOur findings suggest that fascin might be an independent prognostic indicator in the different steps of extracellular matrix invasion. On the other hand, CD44v6 was not a predictive factor in endometrioid cancer.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8511594927206899.

CD24 and Galectin-1 Expressions in Gastric Adenocarcinoma and Clinicopathologic Significance

CD24 and galectin-1 expression in gastric adenocarcinoma and their clinicopathologic significance remained largely unknown. We aimed to evaluate expressions and staining intensities of CD24 and galectin-1 in gastric adenocarcinoma and to investigate the interrelation with clinicopathologic parameters including survival. 93 cases with gastric adenocarcinoma were reevaluated histopathologically and immunohistochemistry was performed with antibodies against CD24 and galectin-1. Staining intensities of both markers in tumor cells and staining intensity of galectin-1 in tumor-associated stromal cells were scored semiquantitatively. The relationship between expression and staining intensity of CD24 and galectin-1 and clinicopathologic variables were assessed. CD24 staining intensity was associated with lymphovascular invasion (p = 0.007), serosal invasion (p = 0.001), stage (p = 0.001) and lymph node metastasis (p = 0.005). Galectin-1 staining intensity in tumor-associated stromal cells was associated with tumor location (p = 0.031), lymphovascular invasion (p = 0.001), perineural invasion (p = 0.001), serosal invasion (p = 0.001), differentiation (p = 0.003), stage (p = 0.001) and lymph node metastasis (p = 0.001). Staining intensity of CD24 (p = 0.019) and gal-1 (p = 0.018) were associated with patient survival. Staining intensity of CD24 in tumor cells and galectin-1 in tumor-associated stromal cells were related with certain clinicopathologic variables. Our findings suggest that these markers are independent prognostic indicators of poor survival and may serve as useful targets for novel therapies.

The effects of dexmedetomidine dosage on cerebral vasospasm in a rat subarachnoid haemorrhage model.

We investigated the effect of two different doses of dexmedetomidine on vasospasm in a rat model of subarachnoid haemorrhage (SAH). SAH was induced by injecting 0.3 mL blood into the cisterna magna in all rat groups except the control (Group C). At 1 hour and 24 hours after SAH, 5 microg/kg dexmedetomidine was given to group D5, and 10 microg/kg dexmedetomidine was given to group D10. No medication was administered to the haemorrhage group (Group H). Malondialdehyde (MDA) and paraoxonase (PON) levels were measured at 48 hours after SAH. Mean wall thickness (MWT), mean luminal diameter (MLD), and proliferating cell nuclear antigen (PCNA) expression of the basilar artery were evaluated. MDA levels and MWT were lower in the dexmedetomidine groups. The lowest MDA levels and MWT were found in Group D10. The MLD was lowest in Group H. PCNA expression was observed only in Group D10. We concluded that dexmedetomidine reduces oxidative stress and vasospasm following SAH in a dose-dependent manner.

The effectiveness of dexmedetomidine in experimental spinal cord injury compared to methylprednisolone in rats.

The present study aimed to investigate the neuroprotective efficacy of dexmedetomidine in a rat experimental spinal cord injury model. The rats (n=40) were equally divided into four groups: G1, G2, G3, and G4. Rats in the G1 group underwent a laminectomy only. For the rats in the G2, G3, and G4 groups, spinal cord injury was induced by placing an aneurysm clip extradurally for 60 s at T10. The rats in G2 did not receive any post-injury treatment. Immediately after trauma was induced, rats in G3 were given methylprednisolone (30 mg/kg) and in G4, dexmedetomidine (10 microg/kg), both intraperitoneally. The rats were sacrificed under anesthesia 24 hours later and 1.5 cm lengths of injured spinal cord were obtained. Malonyldialdehyde values were significantly increased in G2 compared to G1, G3 and G4 (p<0.05). The neuronal cell count in G1 was significantly higher than in G2 and G3 (p=0.0001; p=0.007). G4 had higher cell counts compared to G2 and G3 (p=0.0001; p=0.05). These findings indicated that dexmedetomidine might have neuroprotective effects in spinal cord injury.

Does sildenafil reverse the adverse effects of ischemia on ischemic colon anastomosis: yes, 'no'.

INTRODUCTION Sildenafil may lead an improvement in anastomotic healing of ischemic left colon anastomosis. METHODS Thirty-six male Wistar albino rats were randomized into four experimental groups (n=9 in each group). In group 1, a well-perfused left colonic segment was transected, and free ends were anatomosed. In groups 2, 3 and 4 animals underwent a standardized surgical procedure to induce ischemic left colon anastomosis. Group 2 animals received only tap water. In groups 3 and 4 animals received 10mg/kg/body-weight and 20mg/kg/body-weight sildenafil, single dose a day during 4 days, respectively. Rats were sacrificed on day 4 following operation. Anastomotic integrity, intra-peritoneal adhesion scores, anastomotic bursting pressures and tissue hydroxyproline levels were recorded. Histopathological examination of the anastomosis was also performed. RESULTS There was no statistically significant difference among groups with respect to anastomotic integrity (p=0.142) but ischemia decreased the anastomotic bursting pressure. The mean bursting pressure values were 78.8+/-24.1, 43.3+/-26, 55.1+/-32.4, and 43.3+/-20.4 in groups 1, 2, 3, and 4, respectively. Group 1 had the highest values whereas; there was no statistically significant difference between groups 1 and 3. There was no statistically significant difference among groups 2, 3, and 4 with respect to tissue hydroxyproline levels, adhesion scores and the Chiu scores. The highest inflammatory cell presence in the granulation tissue was detected in group 2, whereas the lowest was detected in group 4 (p=0.0001). The highest fibroblast infiltration in the granulation tissue was detected in group 1 (p=0.045). DISCUSSION Our results showed that 10mg/kg sildenafil decreased the adverse effects of ischemia on the healing of ischemic left colon anastomosis. Additional investigations are needed to confirm the effects of phosphodiesterase-5 inhibitors in ischemic colon anastomosis models.

Expression of adhesion molecules in first trimester spontaneous abortions and their role in abortion pathogenesis.

Background. Early placental development is associated with complex regulatory mechanisms, and molecular communication problems that arise during the developmental process are dangerous for continuation of the pregnancy. As studies on the process of invasion and migration of trophoblast cells have shown the importance of cell–cell and cell–matrix interactions, we examined the effects of adhesion molecules on the mechanism(s) of spontaneous abortions and compared them to elective abortion materials using histopathological and immunohistochemical methods. To the best of our knowledge, this is the first study to investigate adhesion molecules in spontaneous abortions. Methods. Curettage materials from abortions were examined retrospectively in the Department of Pathology, Zonguldak Karaelmas University School of Medicine, Zonguldak, Turkey. CD31/PECAM‐1 (endothelial cell marker), CD44v (variant 3), E‐cadherin, CD54/ICAM‐1, and CD106/VCAM‐1 expression profiles were evaluated by immunohistochemistry, and cellular localization was determined under light microscopy. The results of spontaneous abortions were compared to those of elective abortions. Results. The staining percentages of CD31, CD44, CD106, and E‐cadherin decreased in cases of spontaneous abortion, but CD54 (ICAM‐1) expression increased. Statistically significant differences were detected between spontaneous and elective abortion materials with regard to cytotrophoblasts (CTs), syncytiotrophoblasts (STs), and extravillous trophoblasts (EVTs) with the anti‐CD31 antibody (p = 0.0001). In addition, CD54 (p = 0.007 and p = 0.002) and E‐cadherin (p = 0.002 and p = 0.02) expression in CTs and STs, respectively, were significantly different. Furthermore, CD44 expression (p = 0.003) in decidual (D) cells and CD106 (p = 0.0001) expression in vessels of endometrial (E) and villous tissues were also significantly different. Conclusions. Decreased CD31 expression in CTs that invade the spiral arterioles and mimic E cells in spontaneous abortion cases suggests that CD31/PECAM‐1 is an important molecule in uteroplacental adequacy. Moreover, diminished expression of CD44 in D cells caused impaired stroma–villous connections. Enhancement of ICAM‐1 in placental and invading STs may be useful as a diagnostic marker for patients who may have a tendency to have spontaneous abortions. A down‐regulation of E‐cadherin was observed, which may be responsible for impaired CT differentiation and loss of the pregnancy. Furthermore, decreased VCAM‐1 expression in spontaneous abortions may be consistent with the importance of VCAM‐1 in trophoblast–endothelial cell interactions. Many adhesion molecules are known to be effective in the normal development of a pregnancy, and the analysis of adhesion molecules in spontaneous abortions will provide useful information for clarifying the physiopathology of spontaneous abortions.

Intraobserver and Interobserver Variability of Fuhrman and Modified Fuhrman Grading Systems for Conventional Renal Cell Carcinoma

The Fuhrman nuclear grade is the most widely used grading system for renal cell carcinoma. The aim of this study was to evaluate the intraobserver and interobserver variability of the Fuhrman and modified Fuhrman grading systems for conventional renal cell carcinoma. In this study, five pathologists independently classified 110 cases of conventional renal cell carcinoma according to the Fuhrman and modified (three‐ and two‐tiered) Fuhrman grading systems. The intraobserver and interobserver variability of these systems were assessed using κ statistics. The associations between the Fuhrman and modified Fuhrman grades, pathologic stage and tumor size were determined by correlation analysis. The intraobserver and interobserver combined mean κ values for four‐tiered Fuhrman grading were 0.48 and 0.41, respectively. The highest agreement was detected in two‐tiered modification (including grades 1 + 2 and 3 + 4); the intraobserver and inter‐observer combined mean κ values were 0.67 and 0.62, respectively. Correlations between pathologic stage and tumor size with two‐tiered modification (including grades 1 + 2 and 3 + 4) were greater than those in three‐ and four‐tiered Fuhrman grading. Collapsing the Fuhrman grading into a two‐tiered scheme improved the intraobserver and interobserver reproducibility.

Ectopic pancreas associated with choledochal cyst and multiseptate gallbladder.

Congenital choledochal cyst is a rarely seen malformation of childhood, particularly when associated with multiseptate gallbladder or ectopic pancreas. The current case represents a 15-day-old boy with jaundice. Ultrasonography suggested a cystic lesion, probably of the common bile duct. The patient underwent a total excision of type I choledochal cyst and gallbladder with Roux-en-Y anastomosis, and a wedge biopsy from the liver. Gross examination revealed multiple septa dividing the gallbladder into multiple compartments. The outer and inner surfaces of the choledochal cyst were unremarkable. Microscopically, the cyst wall was composed of dense fibrous tissue with a single layer of cubic to columnar cells constituting the overlying epithelium. Serial sections incidentally revealed ectopic pancreatic tissue lying along the cyst wall characterized by acini, islets, and ductal structures with endocrine cells reactive for chromogranin A. Septa dividing the gallbladder were composed of fibrotic stalks containing smooth muscle fibers. Areas of papillary hyperplasia and intestinal metaplasia of gallbladder epithelium were also noted. The liver biopsy specimen demonstrated the presence of intrahepatic bile ducts, subsequently confirmed by cytokeratin 7. To our knowledge, this case represents the 1st one associated with these 3 entities and only the 2nd choledochal cyst with ectopic pancreatic tissue in its wall.

The Effects of Resveratrol on the Healing of Left Colonic Anastomosis

Introduction: Resveratrol (RSV) is a natural polyphenolic compound found in grape skins and the red wine which improves histological reorganization of the regenerating tissue in dermal wound healing. Since anastomotic healing possesses paramount importance to prevent complications in colorectal surgery, the present study is aimed to evaluate the effect of RSV on the healing of experimental left colonic anastomoses. Methods: Thirty-two male Wistar albino rats were randomized into two groups and subjected to colonic anastomosis. The study group was treated with RSV and the control group received tap water instead. The rats were sacrificed 3 and 7 days postoperatively. Wound complications, intra-abdominal abscesses, and anastomotic leaks and stenosis were recorded. Four types of assessment were performed: bursting pressure, hydroxyproline (OHP) content, histopathology, and biochemical analysis. Results: Compared to the control group, the RSV-treated rats displayed a higher bursting pressure (p <. 001) and anastomotic OHP content (p <. 05)]. RSV treatment leads to significant increase in PON activity at both time points and decrease in malondialdehyde levels on postoperative day 3 (p <. 001). Histopathological analysis revealed that RSV administration leads to a better anastomotic healing in terms of mucosal ischemia, neovascularization, reepithelialization, fibroblast, and lymphocyte infiltration. Conclusion: The study results suggest that exogenous RSV administration exerts a positive effect on experimental colonic wound healing in the rat. Although the precise cellular mechanisms by which RSV enhances anastomotic wound healing is not clear, stimulation of neovascularization, generation of collagen synthesis, inhibition of overinflammation, and restriction of oxidative injury seems to be of paramount importance.