Epithelial Vimentin Expression Research Articles

Single-cell profiling of low-stage endometrial cancers identifies low epithelial vimentin expression as a marker of recurrent disease.

Identification of aggressive low-stage endometrial cancers is challenging. So far, studies have failed to pinpoint robust features or biomarkers associated with risk of recurrence for these patients. Imaging mass cytometry was used to examine single-cell expression of 23 proteins in 36 primary FIGO IB endometrial cancers, of which 17 recurred. Single-cell information was extracted for each tumor and unsupervised clustering was used to identify cellular phenotypes. Distinct phenotypes and cellular neighborhoods were compared in relation to recurrence. Cellular differences were validated in a separate gene expression dataset and the TCGA EC dataset. Vimentin protein expression was evaluated by IHC in pre-operative samples from 518 patients to validate its robustness as a prognostic marker. The abundance of epithelial, immune or stromal cell types did not associate with recurrence. Clustering of patients based on tumor single cell marker expression revealed distinct patient clusters associated with outcome. A cell population neighboring CD8+ T cells, defined by vimentin, ER, and PR expressing epithelial cells, was more prevalent in non-recurrent tumors. Importantly, lower epithelial vimentin expression and lower gene expression of VIM associated with worse recurrence-free survival. Loss and low expression of vimentin was validated by IHC as a robust marker for recurrence in FIGO I stage disease and predicted poor prognosis also when including all patients and in endometrioid patients only. This study reveals distinct characteristics in low-stage tumors and points to vimentin as a clinically relevant marker that may aid in identifying a here to unidentified subgroup of high-risk patients. A full list of funding that contributed to this study can be found in the Acknowledgements section.

Correlation between epithelial-mesenchymal transition and collagen quality in oral dysplasia and squamous cell carcinoma

Epithelial-mesenchymal transition (EMT) enhances the invasive ability, providing an explanation for the mechanism of tumor metastasis. The stiffness of the stromal extracellular matrix collagen can regulate the epithelial cell growth and migration in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). Objectives: to study the epithelial expression of Vimentin as a marker for EMT and to elucidate the nature of collagen in OED and OSCC and finally to correlate EMT to collagen quality in these lesions. Material and methods: the area fraction of immunohistochemical epithelial expression of Vimentin and color polarization of picrosirius red stained collagen fibers were detected in ten specimens of each grade of OED and OSCC as well as normal oral mucosa followed by statistical analysis. Results: a statistically significant increase in the median area fractions of epithelial Vimentin expression and yellow-green fibers were detected as the grade of OED and OSCC progressed. Spearman’s correlation coefficient revealed a statistically significant direct correlation between epithelial Vimentin expression and yellow-green fibers in these lesions. Conclusion: there was a statistically significant increase in EMT and decrease in the collagen quality with the advance of OED and dedifferentiation of the neoplasm. The significant inverse correlation between EMT and collagen quality indicates the role of EMT in stromal collagen quality in these lesions and aid in their prognosis.

Plasticity of endometrial epithelial and stromal cells-A new approach towards the pathogenesis of equine endometrosis.

Equine endometrosis, a frequent cause of subfertility, is characterized by periglandular fibrosis, and no treatment exists. Endometrial biopsies not only contain diseased glands, but also contain healthy glands and stroma. Myoepithelial (ME) and myofibroblastic (MF) markers are calponin, smooth muscle actin (SMA), desmin and glial fibrillary acidic protein (GFAP). Epithelial vimentin expression indicates epithelial to mesenchymal transition (EMT). The aim of this immunohistochemical study was to investigate whether biopsies with endometrosis express MF and ME markers and vimentin. Compared to healthy areas, significantly higher percentages of endometrotic glands were lined by calponin- and vimentin-positive epithelial cells, whereas periglandular fibrosis contained significantly higher percentages of stromal cells positive for vimentin, desmin and SMA and significantly less calponin-positive stromal cells. The rare GFAP expression was restricted to endometrotic glands. Of these, the most frequent features of endometrotic glands were higher percentages of SMA- and vimentin-positive stromal cells and the prominent epithelial calponin staining that occurred in 100%, 93% and 95% of examined biopsies. Results indicate plasticity of equine endometrial epithelial and stromal cells. Particularly, endometrotic glands show evidence for ME differentiation and EMT. The different expression of MF markers between stromal cells from healthy and endometrotic areas suggests functional differences. The characteristic changes in the expression of SMA, vimentin and calponin between endometrotic glands and healthy areas can be helpful to confirm early stages of endometrosis. The characterization of cellular differentiation may help to decipher the pathogenesis of endometrosis and could lead to therapeutic strategies.

Distal renal tubules are deficient in aggresome formation and autophagy upon aldosterone administration.

Prolonged elevations of plasma aldosterone levels are associated with renal pathogenesis. We hypothesized that renal distress could be imposed by an augmented aldosterone-induced protein turnover challenging cellular protein degradation systems of the renal tubular cells. Cellular accumulation of specific protein aggregates in rat kidneys was assessed after 7 days of aldosterone administration. Aldosterone induced intracellular accumulation of 60 s ribosomal protein L22 in protein aggregates, specifically in the distal convoluted tubules. The mineralocorticoid receptor inhibitor spironolactone abolished aldosterone-induced accumulation of these aggregates. The aldosterone-induced protein aggregates also contained proteasome 20 s subunits. The partial de-ubiquitinase ataxin-3 was not localized to the distal renal tubule protein aggregates, and the aggregates only modestly colocalized with aggresome transfer proteins dynactin p62 and histone deacetylase 6. Intracellular protein aggregation in distal renal tubules did not lead to development of classical juxta-nuclear aggresomes or to autophagosome formation. Finally, aldosterone treatment induced foci in renal cortex of epithelial vimentin expression and a loss of E-cadherin expression, as signs of cellular stress. The cellular changes occurred within high, but physiological aldosterone concentrations. We conclude that aldosterone induces protein accumulation in distal renal tubules; these aggregates are not cleared by autophagy that may lead to early renal tubular damage.

Tumour Epithelial Vimentin Expression in Canine Cutaneous Squamous Cell Carcinoma

Tumour Epithelial Vimentin Expression in Canine Cutaneous Squamous Cell Carcinoma

The equine endometrosis: New insights into the pathogenesis

This paper describes the histomorphological and immunohistochemical characterisation of phenotypic variations of endometrosis as well as potential etiological factors which may influence disease progression. In total, 779 endometrial biopsies were examined. These biopsies were taken in the breeding and non-breeding season ( n = 509), on defined days during the estrous cycle ( n = 70) and before and after experimentally induced bacterial endometritis ( n = 200). In addition to conventional histopathology, selected biopsies were investigated using alcianblue staining as well as immunohistochemical methods for the detection of steroid hormone receptors, Ki-67-antigen, vimentin, desmin, fibronectin, smooth-muscle-α-actin and laminin. The equine endometrosis can be divided into a destructive and a non-destructive form. Based on the morphology of the stromal cells involved, an active or inactive state can be distinguished in fibrotic foci. In all types of endometrosis, fibrotic stromal cells show a distinctly reduced expression of steroid hormone receptors in comparison to the intact stroma, indicating their dedifferentiation. However, the steroid hormone receptor expression of involved glandular epithelia seems to depend on the activity of the fibrosis. These results suggest an independency of all fibrotic foci from the hormonal control mechanism of the uterus. The characteristical features of destructive endometrosis are a large number of smooth-muscle-α-actin containing myofibroblasts, a pronounced epithelial vimentin expression, excessive extracellular matrix accumulation and a progressive alteration of the basal lamina. Furthermore, the frequently seen cystic glandular dilatation and mechanical destruction of the uterine glands may occur due to the contractibility of the myofibroblasts involved. As shown in this study, a simultaneous endometritis can cause a temporary activation of fibrotic stromal cells. However, cyclic and seasonal endocrine changes seem to have no effects on progression of the disease. It can be concluded that the various types of endometrosis represent different stages in the fibrotic process, possibly leading to the destruction of the glands and subsequently resulting in the development of a stromal fibrosis.

Propagation protocol for broadleaf arrowheadSagittaria latifoliaWilld. (Alismataceae)

<b>Rationale:</b> In chronic obstructive pulmonary disease (COPD), epithelial changes and subepithelial fibrosis are salient features in the airways. Epithelial to mesenchymal transition (EMT) has been suggested in COPD, mainly in alveolar epithelial cells. <b>Objectives:</b> To evaluate the presence of EMT in the airways and primary air-liquid interface cultures of bronchial epithelial cells (ALI-HBEC) from COPD patients. <b>Methods:</b> Surgical lung tissue of COPD and control patients (n=49) and ALI-HBEC cultures (n=57) were assessed for EMT markers by immunohistochemistry, western blot and real-time qPCR. Mesenchymal functionalities of ALI-HBEC were assayed through fibronectin release and wound repair. <b>Results:</b> The bronchial epithelium from COPD patients, as compared to non-smoker controls, showed increased vimentin expression in large and small airways and correlated with airway obstruction (FEV1, FEV1/VC ratio and DL_CO). In addition, epithelial E-cadherin and zonula occludens-1 (ZO-1) were decreased in large airways. Increased epithelial vimentin expression correlated to subepithelial deposition and basement membrane thickness in COPD thick slices. The COPD bronchial epithelium displayed similar features <i>in vitro</i> and correlated also to lung function. Moreover, COPD ALI-HBEC showed mesenchymal functions such as extra-cellular production of fibronectin and impaired migration during wound repair. <b>Conclusions:</b> The bronchial epithelium from COPD patients displays EMT features in lung tissue, which correlates to disease severity and which are recapitulated in primary cultures in ALI conditions. We propose that this abnormal epithelial programming contributes to peribronchial fibrosis in COPD.

The Critical Time Window for Androgen-Dependent Development of the Wolffian Duct in the Rat

Androgens are thought to separately regulate stabilization and differentiation of the Wolffian duct (WD), but the time windows for these effects are unclear. To address this, fetal rats were exposed to flutamide within either an early window (EW) [embryonic day 15.5 (E15.5) to E17.5], when the WD degenerates in the female, or a later window (LW) (E19.5-E21.5), when the WD morphologically differentiates in the male, or during the full window of WD development (FW) (E15.5-21.5). WDs were examined for abnormalities during fetal (E21.5) or postnatal life, and anogenital distance and prostate presence/absence were recorded. Exposure to FW- or EW-flutamide, but not to LW-flutamide, induced comparable abnormalities in the fetal WD at E21.5, namely reduced WD coiling, reduced cell proliferation, reduced epithelial cell height, altered epithelial vimentin expression, and reduced expression of smooth muscle actin in the WD inner stroma. Exposure to EW- or FW-flutamide, but not to LW-flutamide, resulted in incomplete/absent WDs in more than 50% of males by adulthood, although such abnormalities were infrequent in fetal life. These findings suggest that androgen action during the EW is sufficient to promote WD morphological differentiation several days later. Because the androgen receptor is expressed in the WD stroma but not in the epithelium during this EW, WD differentiation is likely to be dependent on androgen-mediated signaling from the stroma to the epithelium. In conclusion, the critical window for androgen action in regulating WD development in the rat is between E15.5 and E17.5. This window is also important for prostate formation and anogenital distance masculinization.

Immunohistochemical investigation of different cytokeratins and vimentin in the human epididymis from the fetal period up to adulthood

The anatomical distribution of cytokeratins and vimentin was investigated by means of immunohistochemistry in the human epididymis. Epithelial cells of the ductuli efferentes and the corpus epididymidis were positive for cytokeratins and vimentin. The expression of epithelial vimentin decreased toward the cauda epididymidis, whereas cytokeratins remained unchanged. The epithelium of the ductus deferens was negative when antibodies against vimentin were used. With monoclonal antibodies to individual cytokeratins, the presence of cytokeratins 7, 8, 18, and 19 was demonstrated histochemically throughout the epithelium of the epididymis. Monoclonal antibodies specific for cytokeratin 17 allowed immunohistochemical differentiation between the ductuli efferentes and the ductus epididymidis.