Sukru Oguz Ozdamar

Intrauterine growth restriction and placental angiogenesis

BackgroundVascular endothelial growth factor (VEGF), basic-fibroblast growth factor (b-FGF), and endothelial nitric oxide synthase (eNOS) are factors that take part in placental angiogenesis. They are highly expressed during embryonic and fetal development, especially in the first trimester. In this study, we aimed to investigate the role of placental angiogenesis in the development of intrauterine growth restriction (IUGR) by comparing the levels of expression of VEGF-A, b-FGF, and eNOS in normal-term pregnancy and IUGR placentas.MethodsThe expression of VEGF-A, b-FGF, and eNOS was studied using the avidin-biotin-peroxidase method in placental tissues diagnosed as normal (n = 55) and IUGR (n = 55). Results were evaluated in a semi-quantitative manner.ResultsThe expression of all the markers was significantly higher (p < 0.001) in cytotrophoblasts, syncytiotrophoblasts, extravillous trophoblasts, vascular smooth muscle cells, chorionic villous stromal cells, and villous vascular endothelial cells of the IUGR placentas when compared with those collected from normal-term pregnancies.ConclusionIncreased expression of VEGF-A, b-FGF, and eNOS may be the result of inadequate uteroplacental perfusion, supporting the proposal that abnormal angiogenesis plays a role in the pathophysiology of IUGR.

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.

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.

Diagnostic adequacy of surgeon‐performed ultrasound‐guided fine needle aspiration biopsy of thyroid nodules

Surgeon‐performed ultrasonography (US) of thyroid nodules might serve as a potential therapeutic guide to designate accurate surgical or clinical intervention.

Expression of heat shock protein 70 and endothelial nitric oxide synthase in placental tissue of preeclamptic and intrauterine growth-restricted pregnancies

Ischemia, hypoxia, and elevated vascular resistance disturb placental functions by increasing oxidative stress. Heat shock protein 70 (HSP70) is an oxidative stress marker. Endothelial nitric oxide synthase (eNOS) is a nitric oxide enzyme with a key role in pathologic and physiologic angiogenesis and vasculogenesis. This study was performed to investigate the role of oxidative stress in the pathogenesis of preeclampsia and intrauterine growth-restricted (IUGR) pregnancies by comparing the levels of HSP70 and eNOS in placentas from women with these diseases and those with healthy pregnancies. HSP70 and eNOS were examined using the streptavidin-biotin-peroxidase complex technique on formalin-fixed, paraffin-embedded sections from 135 placental villous tissues obtained from normal pregnancies (n=45) and pregnancies complicated with preeclampsia (n=45) and IUGR (n=45). The intensity of labeling in placental tissues with antibodies to HSP70 and eNOS was scored between 0 and 3, using a semiquantitative scale. HSP70 and eNOS levels were increased in the syncytiotrophoblasts, cytotrophoblasts, and extravillous trophoblast cells of preeclamptic and IUGR placentas (P<0.001), compared with normal pregnancies. However, their levels were increased only in the villous endothelial cells of IUGR placentas (P<0.001). Oxidative stress is thought to play an important role in the pathogenesis of preeclampsia and IUGR pregnancies.

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.

Can Lymphatic Vascular Density Be Used in Determining Metastatic Spreading Potential of Tumor in Invasive Ductal Carcinomas

Regional lymph node status is the primary parameter determining treatment strategies and prognoses in breast cancer. Lymphatic vessels in primary tumor tissue play a significant role in lymphatic metastasis. The aim of this study was to investigate the correlation of intra- and peritumoral lymphatic microvessel densities (LVD) with prognostic parameters in breast cancer, including lymphatic invasion (LI). Lymphangiogenesis was investigated using D2-40 monoclonal antibody in 69 invasive ductal carcinoma cases who underwent mastectomy and axillary lymph node dissection. Positively stained microvessels were counted at 400× in dense lymphatic vascular foci (hotspots). Tumor LI was established when at least one neoplastic cell cluster was clearly visible inside a D2-40-positive lymph vessel. Relationships were sought between clinicopathological parameters and mean LVD and LI in primary tumor tissue. Peritumoral LVD was markedly higher than intratumoral LVD (p < 0.001). No significant relationship was found between intratumoral LVD and clinicopathological parameters (p > 0.05). However, significant relationships were detected between peritumoral LVD and LVI [H&E] (p = 0.04), number of lymphatic invasion [n/mm2, D2-40] (p = 0.001), tumor size (p = 0.01), lymph node status (p = 0.03), and tumor stage (p = 0.04). The immunohistochemical determination of LI and LVD can contribute to the prediction of a tumor’s biological behavior in invasive ductal carcinomas. Peritumoral LVD in primary tumor tissue is closely related to parameters influencing the prognosis of a tumor.