Epithelial-To-Mesenchymal Transition and Its Correlation With Clinicopathologic Features in Patients With Urothelial Carcinoma of the Bladder

2017 ◽  
Vol 15 (2) ◽  
pp. e187-e197 ◽  
Author(s):  
Rinni Singh ◽  
Jamal A. Ansari ◽  
Niharika Maurya ◽  
Anil Mandhani ◽  
Vinita Agrawal ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Epithelial To Mesenchymal Transition ◽  
Clinicopathologic Features ◽  
Mesenchymal Transition ◽  
Carcinoma Of The Bladder

scholarly journals Sarcomatoid Urothelial Carcinoma of the Bladder: Analysis of 28 Cases With Emphasis on Clinicopathologic Features and Markers of Epithelial-to-Mesenchymal Transition

2016 ◽  
Vol 140 (6) ◽  
pp. 543-551 ◽  
Author(s):  
Joseph Sanfrancesco ◽  
Jesse K. McKenney ◽  
Mariah Z. Leivo ◽  
Sounak Gupta ◽  
Paul Elson ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Epithelial To Mesenchymal Transition ◽  
Smooth Muscle Actin ◽  
Mesenchymal Transition ◽  
Immunohistochemical Markers ◽  
Not Otherwise Specified ◽  
Cytokeratin 5 ◽  
Aggressive Tumor ◽  
Carcinoma Of The Bladder

Context.—Sarcomatoid urothelial carcinoma (UCa) is a rare but aggressive variant of bladder cancer that can show diagnostic challenges even using ancillary techniques. Objective.—To examine immunohistochemical markers in the context of sarcomatoid UCa, including those associated with epithelial-to-mesenchymal transition. Design.—Twenty-eight cases of sarcomatoid UCa were rereviewed. Clinical outcomes were obtained through database search. Immunohistochemistry for clinical and epithelial-to-mesenchymal transition markers was performed. Results.—All patients had biopsy-proven invasive UCa; 61% (17 of 28) had sarcomatoid UCa at initial diagnosis. A recognizable epithelial component(s) was present in 17 lesions. The sarcomatoid component accounted for 65% of the lesion (average), with heterologous elements present in 3 of 28 cases (11%). The morphologic spectrum of the sarcomatoid element included spindled not otherwise specified, myxoid, pseudoangiosarcomatous, and malignant fibrous histiocytoma–like undifferentiated features. The sarcomatoid component was immunoreactive for pancytokeratin (22 of 26; 85%), p63 (20 of 26; 77%), cytokeratin 903 (17 of 26; 65%), cytokeratin 7 (16 of 26; 62%), GATA3 (16 of 26; 62%), and cytokeratin 5/6 (16 of 26; 62%). STAT-6, CD31, CD34, and HMB45 were all nonreactive, whereas smooth muscle actin often showed at least focal immunoreactivity (22 of 26; 85%). Epithelial-to-mesenchymal transition markers were frequently expressed, including vimentin (26 of 26; 100%), FoxC2 (26 of 26; 100%), SNAIL (23 of 26; 88.5%), and ZEB1 (18 of 26; 69.2%). Follow-up was available for 24 patients (median, 7 months). Sixteen of 28 patients (57%) died of disease (overall mean survival, 9.1 months). The presence of myxoid or chordoid features was associated with reduced survival (P < .05). Conclusions.—Sarcomatoid UCa is an aggressive form of UCa that frequently expresses epithelial-to-mesenchymal transition markers, suggesting a possible mechanism associated with aggressive tumor behavior.

scholarly journals Disabled Homolog 2 (DAB2) Protein in Tumor Microenvironment Correlates with Aggressive Phenotype in Human Urothelial Carcinoma of the Bladder

Diagnostics ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 54
Author(s):  
Yoshitaka Itami ◽  
Makito Miyake ◽  
Sayuri Ohnishi ◽  
Yoshihiro Tatsumi ◽  
Daisuke Gotoh ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Migration Ability ◽  
Clinical Role ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
Carcinoma Of The Bladder ◽  
And Migration ◽  
Related Proteins

Disabled homolog-2 (DAB2) has been reported to be a tumor suppressor gene. However, a number of contrary studies suggested that DAB2 promotes tumor invasion in urothelial carcinoma of the bladder (UCB). Here, we investigated the clinical role and biological function of DAB2 in human UCB. Immunohistochemical staining analysis for DAB2 was carried out on UCB tissue specimens. DAB2 expression levels were compared with clinicopathological factors. DAB2 was knocked-down by small interfering RNA (siRNA) transfection, and then its effects on cell proliferation, invasion, and migration, and changes to epithelial-mesenchymal transition (EMT)-related proteins were evaluated. In our in vivo assays, tumor-bearing athymic nude mice subcutaneously inoculated with human UCB cells (MGH-U-3 or UM-UC-3) were treated by DAB2-targeting siRNA. Higher expression of DAB2 was associated with higher clinical T category, high tumor grade, and poor oncological outcome. The knock-down of DAB2 decreased both invasion and migration ability and expression of EMT-related proteins. Significant inhibitory effects on tumor growth and invasion were observed in xenograft tumors of UM-UC-3 treated by DAB2-targeting siRNA. Our findings suggested that DAB2 expression was associated with poor prognosis through increased oncogenic properties including tumor proliferation, migration, invasion, and enhancement of EMT in human UCB.

scholarly journals The Prognostic Value of some Epithelial-Mesenchymal Transition Markers and Metastasis-Related Markers in Human Transitional Cell Carcinoma of the Bladder

2018 ◽  
Vol 15 (3) ◽  
pp. 244-252
Author(s):  
Baghdad Science Journal
Keyword(s):  
Transitional Cell Carcinoma ◽  
Cell Carcinoma ◽  
Expression Pattern ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Transitional Cell ◽  
Mesenchymal Transition ◽  
Carcinoma Of The Bladder ◽  
E Cadherin

Recent reports provided evidence that epithelial to mesenchymal transition (EMT) and some matrix metalloproteinases (MMPs) contribute to the invasion and metastasis of cancer cells. This study investigated the expression pattern of some EMT markers (E-cadherin and Vimentin) and some MMPs (MMP-2 and MMP-9) in transitional cell carcinoma (TCC). Fifty five paraffin embedded biopsies were included in this study. Expression pattern of E-cadherin and Vimentin was evaluated by immunohistochemistry while cytoplasmic mRNA expression of both MMP-2 and MMP-9 were determined by in situ hybridization. The expression of all markers were significantly increased with the increase of patient's age (? 50 years), and furthermore an increase in men expression when compared to women. Interestingly, all healthy tissues showed positive E-cadherin expression while they did not show any expression of Vimentin, MMP-2 and MMP-9. E-cadherin expression decreased, whereas expression of Vimentin increased according to the grade and stage of the tumor. Similarly, both MMP-2 and MMP-9 expression were increased with the progression of TCC. The current study conclude that a decrease in E-cadherin together with increased Vimentin, MMP-2 and MMP-9 are significant markers that correlate with poor prognosis of TCC.

scholarly journals BGJ398, A Pan-FGFR Inhibitor, Overcomes Paclitaxel Resistance in Urothelial Carcinoma with FGFR1 Overexpression

2018 ◽  
Vol 19 (10) ◽  
pp. 3164 ◽  
Author(s):  
Se Kim ◽  
Haram Ryu ◽  
Chan-Young Ock ◽  
Koung Suh ◽  
Ji Lee ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Epithelial To Mesenchymal Transition ◽  
Single Agent ◽  
D1 Protein ◽  
Growth Factor Receptor ◽  
Mesenchymal Transition ◽  
Effective Strategies ◽  
Cycle Arrest ◽  
Platinum Based Chemotherapy ◽  
Cyclin D1 Protein

Paclitaxel (PTX) is commonly used to treat urothelial carcinoma (UC) after platinum-based chemotherapy has failed. However, single-agent taxane therapy is not sufficient to inhibit tumor progression and drug resistance in advanced UC. Epithelial-to-mesenchymal transition (EMT) induced by fibroblast growth factor receptor (FGFR)1 signaling has been proposed as a mechanism of PTX resistance, but it is unclear whether this can be overcome by FGFR1 inhibition. The present study investigated whether FGFR1 overexpression contributes to PTX resistance and whether FGFR inhibition can enhance PTX efficacy in UC. The effects of PTX combined with the FGFR inhibitor BGJ398 were evaluated in UC cell lines by flow cytometry; Western blot analysis; cell viability, migration, and colony forming assays; and RNA interference. PTX+BGJ398 induced cell cycle arrest and apoptosis in UC cells with mesenchymal characteristics was accompanied by downregulation of cyclin D1 protein and upregulation of gamma-histone 2A family member X and cleaved poly(ADP-ribose) polymerase. Additionally, PTX+BGJ398 synergistically suppressed UC cell migration and colony formation via regulation of EMT-associated factors, while FGFR1 knockdown enhanced the antitumor effect of PTX. These findings provide a basis for development of effective strategies for overcoming PTX resistance in UC through inhibition of FGFR1 signaling.

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