Histopathological and Immunohistochemical Evaluation of Pannus Tissue in Patients with Prosthetic Valve Dysfunction.

BACKGROUND: Prosthetic valve dysfunction due to pannus formation is a rare but serious complication. Currently, limited data are available concerning the pathogenesis and immunohistochemical properties of pannus. The study aim was to investigate the morphological, histopathological and immunohistochemical characteristics of pannus formation in patients with prosthetic valve dysfunction. METHODS: A total of 35 patients (10 males, 25 females; mean age 44 ± 16 years) who had undergone re-do valve surgery due to prosthetic valve obstruction was enrolled in the study. Immunohistochemical studies were aimed at evaluating the expression of alphasmooth muscle actin (α-SMA) and desmin in myofibroblasts and smooth muscle cells; epithelial membrane antigen (EMA) in epithelial cells; and CD34, Factor VIII and vascular endothelial growth factor (VEGF) in endothelial cells. Matrix metalloproteinases (MMPs) -2 and -9, and transforming growth factor-beta (TGF-ß) were used to demonstrate cytokine release from macrophages, leukocytes, fibroblasts and myofibroblasts. RESULTS: Pannus appeared as a tough and thick tissue hyperplasia which began from outside the suture ring in the periannular region and extended to the inflow and outflow surfaces of the prosthetic valves. Histopathological analysis showed the pannus tissue to consist of chronic inflammatory cells (lymphocytes, plasma cells, macrophages and foreign body giant cells), spindle cells such as myofibroblasts, capillary blood vessels and endothelial cells laying down the lumens. Calcification was present in the pannus tissue of 19 explanted prostheses. Immunohistochemical studies revealed positive α-SMA expression in all patients, whereas 60.5% of patients were positive for desmin, 50% for EMA, 42.1% for VEGF, 39.5% for TBF-ß, 42.1% for MMP-2, 86.8% for CD34, and 97.4% for Factor VIII. MMP-9 was negative in all patients. CONCLUSIONS: Pannus tissue appears to be formed as the result of a neointimal response in periannular regions of prosthetic valves that consist of periannular tissue migration, myofibroblast and extracellular matrix proliferation with vascular components. It is a chronic active process in which mediators such as TGF-ß, VEGF and MMP-2 play roles in both matrix formation and degradation.

Expression of Cox-2 and Bcl-2 in Paget's disease of the breast.

BACKGROUND: Paget's disease (PD) is a rare form of intraepithelial adenocarcinoma that involves breast and extramammarian tissues. It is often associated with ductal carcinoma in situ and/or invasive ductal cancer. Molecular pathways that play a role in development of Paget's disease are stil unclear. Expression patterns of Cox-2 and bcl-2 were therefore assessed. MATERIALS AND METHODS: Patients with a histopathological diagnosis of Paget's disease were included in this study. Patient files were analysed retrospectively. RESULTS: Invasive cancer was diagnosed in 35 (76.1%) of the patients, 7 (15.2%) had ductal carcinoma in situ and 4 (8.7%) patients had no associated neoplasm. Twenty four (52.2%) patients showed COX-2 expression in Paget cells whereas no expression was seen in 22 (47.8%) patients. No relation was found between COX-2 expression and the lesion underlying Paget's disease (p=0.518). Bcl-2 expression in Paget cells was found positive in 12 (26.1%) and negative in 27 (58,7%) cases. There was no relation between Bcl-2 expression and the lesion accompanying Paget's disease (p=0.412). No relation was observed between COX-2 expression and Bcl-2 expression (p=0.389). CONCLUSIONS: In breast cancer, COX-2 expression is associated with poor prognostic factors. As COX-2 expression increases the tendency to metastasize also increases. In our study we found a significantly high COX-2 expression in Paget's disease of the breast. We suggest that COX-2 expression and inflammatory processes may play a role in pathogenesis of the Paget's disease of the breast.

The role of insulin-like growth factor 1 in the development of benign and malignant thyroid nodules.

OBJECTIVE: This study aims to investigate the role of IGF-1 in the development of nodular thyroid disease. MATERIAL AND METHODS: A total number of 100 consecutive patients operated for nodular thyroid disease in our institution were included in this prospective study. In addition to classical pathological examinations, nodules and extranodular healthy tissues were sampled and immunochemically stained for IGF-1. The materials were independently evaluated using an Allred Scoring System ranging from 0 to 8. If the score was ≥1, the tissue was accepted as IGF-1 positive. RESULTS: IGF-1 positivity was observed in 88% and 58% of the samples obtained from nodules and extranodular healthy tissues, respectively. Allred 8-unit scores were higher in benign nodules (n=89; 4.1±2.3) and papillary carcinomas (n=7; 6.7±1.3), than in extranodular healthy tissues in the same patients (2.3±2.3 and 3.3±1.9, respectively); and higher in papillary carcinomas than in benign nodules, when the scores were compared to each other (p<0.01 for all comparisons). CONCLUSIONS: Allred 8-unit scores for IGF-1 increase in the presence of benign thyroid nodules, papillary cancer. The results of our study support the findings of previous studies demonstrating the role of IGF-1 in the development of thyroidal nodules.