Purpose: Epithelial to mesenchymal transition (EMT) is reportedly an important transition in cancer progression in which the underlying cellular changes have been identified mainly using in vitro models. In this study, we examined the expression pattern of EMT markers in vivo and determinedtheoccurrenceandclinicalsignificanceof these eventsinaseriesofbladdercarcinomas. Experimental Design: Eight hundred and twenty-five tumor samples from 572 bladder cancer patients were assembled in 10 tissue microarrays. Paraffin sections from each tissue microarray were subjected to antigen retrieval and processed by immunohistochemistry for the expression of E-cadherin, plakoglobin, h-catenin, N-cadherin, and vimentin. Results: Pathologic expression of E-cadherin, h-catenin, plakoglobin, and vimentin were associated with the clinicopathologic variables of grade and stage with only the cytoplasmic localization of plakoglobin found associated with lymph node status. Associations between the aforementioned markers were found significant as determined by the Spearman correlation coefficient with N-cadherin showing no associations in this analysis. In univariate survival analysis involving patients who underwent cystectomy, the reduction or loss of plakoglobin significantly influenced overall survival (P = 0.02) in which the median time to death was 2 years compared with 4 years when a normal level of plakoglobin was recorded. When the analysis was done for cancer-specific survival, low levels of both plakoglobin (P = 0.02) and h-catenin (P = 0.02) significantly influenced survival. Conclusion: The putative markers of EMTdefined within a panel of bladder carcinoma cell lines were recorded in vivo, frequently associated with tumors of high grade and stage. Although multivariate analysis showed no significant influence of the EMT biomarkers on survival, alterations associated with plakoglobin were identified as significant prognostic features in these tumors. Epithelial to mesenchymal transition (EMT) is a process thatwas first observed in embryonic development (1 -3) and has more recently been implicated as an underlying event in neoplastic progression (4 -7). To date, the definition and occurrence of EMT in in vivo tumorigenesis remains controversial (6, 8); however, the conceptual framework embracing loss of epithelial markers and gain of mesenchymal markers has been reportedly associated with numerous cancers (9 -11), often identified in cell lines established from tumors representing different grades and stage (10,12). In this way, the discontinuous progression model observed within a panel of cell lines of common tissue origin may be closely linked to the differentiation status of cells. In most cases, the projected transition between epithelial and mesenchymal phenotypes is accompanied by increased motility and invasive potential.With the advent of the establishment of in vitro models of EMT, elicited by the action of different factors on alternative cell types (13 -18), the existence of EMT in progression becomes mo...

The CM demonstrated significant bactericidal activity compared with UM. Nanocrystalline silver particles may decrease the incidence of postoperative prosthetic mesh infections and be useful as a coating for other prosthetic materials.

OBJECTIVE To identify the frequency of change in the expression and localization of p120ctn in bladder tumours and its association with clinical outcomes, and to investigate the potential role of p120ctn in the migratory and invasive behaviour of bladder carcinoma cells. MATERIALS AND METHODS In all, 425 superficial tumour specimens (Ta, Tis and T1) and 305 invasive (T2–T4) tumour specimens from 534 patients were assembled in 10 tissue microarrays. P120ctn immunostaining was scored for intensity and cellular localization and correlated with clinical variables and survival analysis. Knockdown of p120ctn was achieved using small‐interference RNA (siRNA) followed by the assessment of migration and invasion behaviour in standard in vitro assays. RESULTS The expression levels of p120 catenin inversely correlated with pathological tumour stage (P < 0.001), histological grade (P < 0.001), presence of lymphovascular invasion (P = 0.02) but not lymph node (LN) involvement (P = 0.17). Non‐membranous localization of p120ctn correlated with stage (P < 0.001), grade (P < 0.001), lymphovascular invasion (P = 0.04) and LN‐positive disease (P = 0.02). A low expression level of p120ctn was linked to a poor outcome in cancer‐specific survival analysis. Knockdown of p120ctn using siRNA resulted in a significant reduction in the migration and invasive potential of bladder carcinoma cells. CONCLUSIONS Our findings suggest that p120ctn acts as a prognostic factor in bladder tumours and has a primary role to play in the migratory and invasive behaviour of bladder carcinoma cells.

Although mutations in the coding region of epidermal growth factor receptor are rare in invasive bladder tumors, differential sensitivity to erlotinib was recorded within a panel of cell lines. Maintenance of the phosphorylation status of Akt in the presence of erlotinib along with epithelial-to-mesenchymal transition correlates with insensitivity to growth inhibition in bladder carcinoma cell lines. Even in the absence of epidermal growth factor receptor mutations erlotinib shows potential as a therapeutic agent for the treatment of bladder cancer.

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