Immunoexpression of Snail, Twist1 and Slug in clear cell renal cell carcinoma.

Clear cell renal cell carcinomas (ccRCC) represent about 80% of the malignant neoplasia with this localization. Snail, Twist1 and Slug are transcription factors and play a central role in the epithelial-mesenchymal transition (EMT), which is involved in the progression of renal cell carcinoma (RCC). In this study, we analyzed the immunoexpression of these transcription factors in 50 cases of ccRCC, in relation to histopathological aggressiveness parameters of the lesions. The results indicated the association of Snail and Twist1 expression with high Fuhrman grade, as well as the association of Slug expression with low Fuhrman grade. The immunoexpression of Snail and Twist1 was significantly superior for advanced stages and Slug was overexpressed in early stages of ccRCC. Our study supports the usefulness of the Snail, Twist1 and Slug expression for the appreciation of aggressiveness in ccRCC, the panel being attractive for targeted therapy.

Immunoexpression of E-cadherin, Snail and Twist in colonic adenocarcinomas.

Epithelial-mesenchymal transition (EMT) is an important mechanism in tumor progression. Snail is a transcription factor, expressed in cells which have undergone almost complete EMT and have left the tumor, and Twist is considered important in the process of metastasis, both playing a major role in EMT by indirect inhibition of E-cadherin. The study analyzed the immunoexpression of E-cadherin, Snail and Twist in 46 cases of colonic carcinomas in comparison with some histopathological prognostic factors. The quantification of reactions was done by using a composite score (CS) resulted from multiplying the percentage of marked cells with the intensity of immunostaining. The majority of cases were moderately differentiated tumors, corresponded to stage III, with vascular and perineural invasion. All cases presented positive cytoplasmic and nuclear signals for Snail and Twist. The immunostaining for both markers was intense, with the highest values of CS in G2 and G3 advanced, invasive vascular colonic carcinomas, in comparison with G1, early stage lesions. We found positive significant linear correlation of Snail and Twist expression. The results obtained indicate the implication of Snail and Twist in colonic carcinoma aggressiveness, useful aspect in the oncological evaluation of patients and guided therapy.

Epithelial-glial transition in an atypical meningioma - a case report.

Atypical meningiomas with a mixed glial-epithelial phenotype are rare reports, and here we described an aggressive case on which double immunofluorescence ascertained the co-expression of epithelial membrane antigen (EMA) with glial fibrillary acidic protein (GFAP) in the same tumor cells. A 62-year-old female presented with acute intracranial hypertension symptoms occurred over the last 24 hours, muscle weakness on the right side, cerebellar dysarthria, and wide base gate. Magnetic resonance imaging (MRI) examination showed a right cerebellar hemisphere non-homogenous tumor, with intense gadophylia, diffuse contours, and necrotic inner areas. There were also scar-like areas at the level of the left cerebellar hemisphere, and the patient recalled a previous surgical intervention at the age of 6 years old without further diagnostic data. The patient suffered an ischemic event in the brain stem and died shortly after the surgical removal of the tumor. Histopathology revealed an epithelial-like tumor with moderately pleomorphic and elongated cells arranged in fascicles, rare necrotic areas, and a few proliferating multilayered vessels structures. Immunohistochemistry (IHC) revealed variable EMA positivity, intense vimentin staining, rare GFAP-positive intra-tumor areas, a moderate expression for cytokeratin 8/18, reduced labeling for an anti-progesterone receptor (PrgR) antibody, cluster of differentiation (CD) 10 negativity, and a high Ki-67 proliferating index of around 40%. The case was deemed as an atypical meningioma, and interestingly, a double IHC for GFAP∕EMA revealed a strong colocalization of the two markers in the tumor mass. Although extremely rare, the reports of meningiomas expressing a mixed epithelial∕glial profile might be connected with their aggressive evolution. Double IHC might help in predicting the evolution of these cases and determine which patients should benefit from closer surveillance.

Histological factors that predict the liver fibrosis in patients with chronic hepatitis C.

In chronic hepatitis, pathologies reveal a prominent inflammatory infiltrate portal consisting mostly of lymphocytes and plasma cells invading the portal spaces, although one can also identify macrophages, neutrophils or eosinophils. In all the forms of chronic hepatitis, fibrosis starts in the portal area, namely periportally, subsequently extends towards the lobules to the central veins, causing septa, followed by fibrosis. We studied 52 patients with chronic hepatitis C, who underwent a hematological, biochemical, virological and histopathological investigation. We found that the severity degree of the portal inflammation was in direct relation to the hepatitis activity index (HAI) and to the degree of fibrosis. The portal inflammation is dependent to the degree of fibrosis. The degree of inflammation significantly changes the distribution of cases with different degrees of fibrosis (chi-square p=0.00011 <0.001). Periportal inflammation, periportal necrosis and focal necrosis are the morphological aspects of the necroinflammatory process best correlated to the occurrence and development of fibrosis.

Heterogeneity of collagen secreting cells in gingival fibrosis--an immunohistochemical assessment and a review of the literature.

AIM: In this work, we compared the histological features of the gingival lesions clinically diagnosed as fibrotic overgrowths due to various etiologic factors as well as an immunohistochemical assessment of fibroblasts phenotypic heterogeneity using the specific labeling for vimentin, α-smooth muscle actin (α-SMA) and fibroblast specific protein-1 (FSP1). MATERIALS AND METHODS: Tissue samples were obtained from 12 patients clinically diagnosed with fibrotic gingival overgrowth, divided in four groups. Fragments of gingiva were processed for paraffin embedding. Serial sections were used for routine staining Hematoxylin-Eosin, trichromic Masson and Goldner-Szekely, and for immunohistochemical reactions to label vimentin, α-SMA and FSP1 using for signal amplification several techniques (EnVision, LSAB, ABC). RESULTS: Storage of collagen fibers, increase of fibroblast number and frequent presence of inflammatory infiltrate are histological issues of all fibrotic gingival overgrowth. The incidence of granulation tissue varies but the frequency of its presence point the attention to the involvement in collagen metabolism imbalance. Immunostaining for vimentin showed a difference between its expression in samples from different groups. Except the cases of fibrosis induced by orthodontic devices, cells positive for α-SMA were rare. FSP1-positive fibroblasts were the most frequent in all cases from all the groups selected for this study. CONCLUSIONS: The phenotype of fibroblasts is different in gingival fibrosis in relation to the risk factor, at present the most common being vimentin-positive and FSP1-positive fibroblasts. Myofibroblasts are rare in gingival fibrosis, the most numerous being in local lesions caused by wearing orthodontic devices and in syndromic fibromatosis. Further studies are required to elucidate the manner in which the active fibroblasts are recruited in relation to the etiologic factor of gingival overgrowth.

The chick chorioallantoic membrane: a model of short-term study of Dupuytren's disease.

Dupuytren's disease is a progressive fibroproliferative disorder that impairs hand function by altering the normal structures of the palmar fascial bands. Nodules composed almost entirely of myofibroblasts and cords are pathognomonic of Dupuytren's disease. The myofibroblasts express alpha-smooth muscle actin that is especially involved in development of the disease. We aimed to evaluate whether the xenograft of Dupuytren's fibromatosis taken from operating room and transplanted on chick chorioallantoic membrane (CAM) survives with its histological and immunohistological features. Fresh samples obtained from eight patients with Dupuytren's disease were minced and immediately inoculated onto 24 CAMs of 8-day-old chick embryos. The implanted CAMs were examined daily by stereomicroscopy and finally the xenografts were examined and characterized in histological sections using a panel of antibodies. The xenografts were incorporated into the CAMs 6-7 days after transplantation, continued to grow and stimulated angiogenesis in the chick embryo CAMs. The CAMs vessels entered the xenografts and anastomosed with the newly formed xenografts vessels (CD34+ and CD105+) those containing nucleated chick erythrocytes. Myofibroblasts (α-SMA+) and macrophages (CD68+) were readily recognized in the xenograft thickness. We concluded that the xenografts of Dupuytren's fibromatosis transplanted onto chick embryo CAMs continued to develop and preserved the histological and immunohistological features.