scholarly journals Expression of Epithelial-Mesenchymal Transition Related Markers in Plasmacytoid Urothelial Carcinoma of the Urinary Bladder

2020 ◽  
Author(s):  
Shunichiro Nomura ◽  
Yasutomo Suzuki ◽  
Jun Akatsuka ◽  
Yuki Endo ◽  
Akira Shimizu ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Urothelial Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Nippon Medical School ◽  
Female Ratio ◽  
Snail Expression ◽  
Mesenchymal Transition ◽  
Male Female Ratio ◽  
Variant Histology ◽  
E Cadherin

Abstract Background Plasmacytoid urothelial carcinoma (PUC) of the urinary bladder is a variant of urothelial carcinoma that carries a poor prognosis. The epithelial-mesenchymal transition (EMT) has been demonstrated to contribute to tumor progression. As the cause of the increased aggressiveness of PUC is unknown, we investigated PUC and EMT-related marker expression. the proportion of plasmacytoid variant histology Materials and Methods A total of 633 bladder carcinoma cases diagnosed from 2006 to 2014 at the Nippon Medical School Hospital were analyzed. Twelve patients were found to have plasmacytoid histology and diagnosed with PUC. Slides were evaluated for percentage of plasmacytoid variant, and stained for E-cadherin, N-cadherin, Vimentin, Fibronectin and Snail expression. Results The incidence of PUC was 1.9% (12/633). The median patient age at diagnosis was 71 years (range, 60–80 years) and the male-female ratio was 11:1. All but three patients had stage T2b or higher. The median overall survival was 10 months. In 10/12 cases, Snail and N-cadherin were positive. Vimentin was positive in 9/12 cases. Fibronectin was positive in 8/12 cases. While E-cadherin was negative in 10/12 cases. Nine cases showed >10% plasmacytoid component. Eight of the nine patients (88.9%) with >10% plasmacytoid component died. Conclusions The results indicate that PUC may induce EMT and may be associated with high invasion.

scholarly journals Expression of Epithelial-Mesenchymal Transition Related Markers in Plasmacytoid Urothelial Carcinoma of the Urinary Bladder

2020 ◽  
Author(s):  
Shunichiro Nomura ◽  
Yasutomo Suzuki ◽  
Jun Akatsuka ◽  
Yuki Endo ◽  
Akira Shimizu ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Urothelial Carcinoma ◽  
Median Overall Survival ◽  
Epithelial Mesenchymal Transition ◽  
Nippon Medical School ◽  
Female Ratio ◽  
Snail Expression ◽  
Mesenchymal Transition ◽  
Male Female Ratio ◽  
E Cadherin

Abstract Background: Plasmacytoid urothelial carcinoma (PUC) of the urinary bladder is a variant of urothelial carcinoma that carries a poor prognosis. The epithelial-mesenchymal transition (EMT) has been demonstrated to contribute to tumor progression. As the cause of the increased aggressiveness of PUC is unknown, we investigated PUC and EMT-related marker expression. Methods: A total of 633 bladder carcinoma cases diagnosed from 2006 to 2015 at the Nippon Medical School Hospital were analyzed. Twelve patients were found to have plasmacytoid histology and diagnosed with PUC. Slides were evaluated for percentage of plasmacytoid variant, and stained for E-cadherin, N-cadherin, Vimentin, Fibronectin and Snail expression. Results: The incidence of PUC was 1.9% (12/633). The median patient age at diagnosis was 71 years (range, 60–80 years) and the male-female ratio was 11:1. All but three patients had stage T2b or higher. The median overall survival was 10 months. In 10/12 cases, Snail and N-cadherin were positive. Vimentin was positive in 9/12 cases. Fibronectin was positive in 8/12 cases. While E-cadherin was negative in 10/12 cases. Nine cases showed >10% plasmacytoid component. Eight of the nine patients (88.9%) with >10% plasmacytoid component died.Conclusions: The results indicate that PUC may induce EMT and may be associated with high invasion.

scholarly journals Expression of Epithelial-Mesenchymal Transition Related Markers in Plasmacytoid Urothelial Carcinoma of the Urinary Bladder

2020 ◽  
Author(s):  
Shunichiro Nomura ◽  
Yasutomo Suzuki ◽  
Jun Akatsuka ◽  
Yuki Endo ◽  
Akira Shimizu ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Urothelial Carcinoma ◽  
Median Overall Survival ◽  
Epithelial Mesenchymal Transition ◽  
Nippon Medical School ◽  
Female Ratio ◽  
Snail Expression ◽  
Mesenchymal Transition ◽  
Male Female Ratio ◽  
E Cadherin

Abstract Background Plasmacytoid urothelial carcinoma (PUC) of the urinary bladder is a variant of urothelial carcinoma that carries a poor prognosis. The epithelial-mesenchymal transition (EMT) has been demonstrated to contribute to tumor progression. As the cause of the increased aggressiveness of PUC is unknown, we investigated PUC and EMT-related marker expression. Methods A total of 633 bladder carcinoma cases diagnosed from 2006 to 2015 at the Nippon Medical School Hospital were analyzed. Twelve patients were found to have plasmacytoid histology and diagnosed with PUC. Slides were evaluated for percentage of plasmacytoid variant, and stained for E-cadherin, N-cadherin, Vimentin, Fibronectin and Snail expression. Results The incidence of PUC was 1.9% (12/633). The median patient age at diagnosis was 71 years (range, 60–80 years) and the male-female ratio was 11:1. All but three patients had stage T2b or higher. The median overall survival was 10 months. In 10/12 cases, Snail and N-cadherin were positive. Vimentin was positive in 9/12 cases. Fibronectin was positive in 8/12 cases. While E-cadherin was negative in 10/12 cases. Nine cases showed >10% plasmacytoid component. Eight of the nine patients (88.9%) with >10% plasmacytoid component died. Conclusions The results indicate that PUC may induce EMT and may be associated with high invasion.

scholarly journals Plasmacytoid urothelial carcinoma of renal pelvis with positive zinc finger E–box–binding homeobox 1: a case report

2020 ◽  
Author(s):  
Atsuko Takada-Owada ◽  
Yumi Nozawa ◽  
Masato Onozaki ◽  
Shuhei Noda ◽  
Tsengelumaa Jamiyan ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Zinc Finger ◽  
Renal Pelvis ◽  
Plasma Cells ◽  
Epithelial Mesenchymal Transition ◽  
Resected Specimen ◽  
Mesenchymal Transition ◽  
E Box ◽  
Tumor Transformation ◽  
E Cadherin

Abstract BackgroundThe tumor transformation mechanism of a plasmacytoid urothelial carcinoma remains unexplained. We describe the case of a plasmacytoid urothelial carcinoma of the renal pelvis in which the expression of zinc finger E–box–binding homeobox 1 (ZEB1), a key nuclear transcription factor in an epithelial–mesenchymal transition, is involved in tumor transformation.Case presentationThe patient had a left nephrectomy with the clinical diagnosis of left pelvic renal cancer. The resected specimen showed that the tumor surface comprised a noninvasive papillary urothelial carcinoma with the carcinoma in situ, and the invasive area comprised a plasmacytoid urothelial carcinoma characterized by the presence of single dyscohesive malignant cells that resembled plasma cells in a loose myxoid stroma. The noninvasive urothelial carcinoma was positive for cytokeratin and E–cadherin, and negative for vimentin and ZEB1. In contrast, the invasive plasmacytoid urothelial carcinoma was positive for cytokeratin and also vimentin and ZEB1, and negative for E–cadherin. Additionally, this component was immunoreactive for CD138 and CD38 that are immunohistochemical markers for plasma cells.ConclusionWe suggest that ZEB1 is involved in the plasmacytoid transformation by repressing the E–cadherin in a plasmacytoid urothelial carcinoma.

scholarly journals Plasmacytoid urothelial carcinoma of renal pelvis with positive zinc finger E–box–binding homeobox 1: a case report

2020 ◽  
Author(s):  
Atsuko Takada-Owada ◽  
Yumi Nozawa ◽  
Masato Onozaki ◽  
Shuhei Noda ◽  
Tsengelumaa Jamiyan ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Zinc Finger ◽  
Renal Pelvis ◽  
Plasma Cells ◽  
Epithelial Mesenchymal Transition ◽  
Resected Specimen ◽  
Mesenchymal Transition ◽  
E Box ◽  
Tumor Transformation ◽  
E Cadherin

Abstract BackgroundThe tumor transformation mechanism of a plasmacytoid urothelial carcinoma remains unexplained. We describe the case of a plasmacytoid urothelial carcinoma of the renal pelvis in which the expression of zinc finger E–box–binding homeobox 1 (ZEB1), a key nuclear transcription factor in an epithelial–mesenchymal transition, is involved in tumor transformation.Case presentationThe patient had a left nephrectomy with the clinical diagnosis of left pelvic renal cancer. The resected specimen showed that the tumor surface comprised a noninvasive papillary urothelial carcinoma with the carcinoma in situ, and the invasive area comprised a plasmacytoid urothelial carcinoma characterized by the presence of single dyscohesive malignant cells that resembled plasma cells in a loose myxoid stroma. The noninvasive urothelial carcinoma was positive for cytokeratin and E–cadherin, and negative for vimentin and ZEB1. In contrast, the invasive plasmacytoid urothelial carcinoma was positive for cytokeratin and also vimentin and ZEB1, and negative for E–cadherin. Additionally, this component was immunoreactive for CD138 and CD38 that are immunohistochemical markers for plasma cells.ConclusionWe suggest that ZEB1 is involved in the plasmacytoid transformation by repressing the E–cadherin in a plasmacytoid urothelial carcinoma.

scholarly journals Glycogen synthase kinase-3 is an endogenous inhibitor of Snail transcription

2005 ◽  
Vol 168 (1) ◽  
pp. 29-33 ◽  
Author(s):  
Robin E. Bachelder ◽  
Sang-Oh Yoon ◽  
Clara Franci ◽  
Antonio García de Herreros ◽  
Arthur M. Mercurio
Keyword(s):  
Epithelial Cells ◽  
Epithelial Mesenchymal Transition ◽  
Glycogen Synthase ◽  
Normal Breast ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Small Interfering Rnas ◽  
Snail Expression ◽  
Mesenchymal Transition ◽  
E Cadherin

We report that the activity of glycogen synthase kinase-3 (GSK-3) is necessary for the maintenance of the epithelial architecture. Pharmacological inhibition of its activity or reducing its expression using small interfering RNAs in normal breast and skin epithelial cells results in a reduction of E-cadherin expression and a more mesenchymal morphology, both of which are features associated with an epithelial–mesenchymal transition (EMT). Importantly, GSK-3 inhibition also stimulates the transcription of Snail, a repressor of E-cadherin and an inducer of the EMT. We identify NFκB as a transcription factor inhibited by GSK-3 in epithelial cells that is relevant for Snail expression. These findings indicate that epithelial cells must sustain activation of a specific kinase to impede a mesenchymal transition.

scholarly journals Gastrointestinal Carcinoma with Plasmacytoid Morphology: Positivity for c-MET, Arylsulfatase, and Markers of Epithelial-Mesenchymal Transition, as Indicators of Aggressivity

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Zsolt Kovacs ◽  
Simona Gurzu ◽  
Calin Molnar ◽  
Mihaela Sincu ◽  
Laura Banias ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Tyrosine Kinases ◽  
Nuclear Translocation ◽  
Epithelial Mesenchymal Transition ◽  
Case Series ◽  
Surgical Excision ◽  
Gastrointestinal Carcinoma ◽  
Mesenchymal Transition ◽  
Gastrointestinal Carcinomas ◽  
E Cadherin

Background. Plasmacytoid urothelial carcinoma is a rare and aggressive histologic variant of high-grade carcinoma of the urinary bladder. Few than 250 cases have been reported in the urinary bladder till January 2019. In this paper, a case series of unusual gastrointestinal carcinomas with plasmacytoid morphology was included. Only one similar case of the stomach was previously published and no such cases were found in colon. Methods. We present the complex immunoprofile, using a panel of 39 biomarkers, of the largest group of primary gastrointestinal carcinomas with plasmacytoid morphology reported in literature (one from upper rectum and six from stomach). Results. All of the seven cases showed lymph node metastases and only one survived over 25 weeks after surgical excision. The indicators of aggressivity were age (over 60), advanced stage (from IIIA to IV), E-cadherin negativity, and vimentin positivity. The immunoprofile indicated unfavorable prognosis for mesenchymal-type carcinomas (negativity for E-cadherin and positivity for vimentin, with membrane to nuclear translocation or negativity of β-catenin). The survivor showed an “epithelial-type adenocarcinoma with plasmacytoid dedifferentiation”, with membrane positivity for E-cadherin and β-catenin and vimentin negativity. All of the cases expressed c-MET and were negative for HER-2. Conclusions. Primary carcinoma with plasmacytoid morphology is a dedifferentiated variant of adenocarcinoma or poorly cohesive carcinomas. Vimentin positive dedifferentiated-poorly cohesive carcinomas should be considered as mesenchymal-type highly malignant carcinomas. This rare histologic variant of gastrointestinal cancer might respond to anti-c-MET tyrosine kinases.

scholarly journals Plasmacytoid urothelial carcinoma of renal pelvis with positive zinc finger E–box–binding homeobox 1: a case report

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Atsuko Takada-Owada ◽  
Yumi Nozawa ◽  
Masato Onozaki ◽  
Shuhei Noda ◽  
Tsengelmaa Jamiyan ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Zinc Finger ◽  
Renal Pelvis ◽  
Plasma Cells ◽  
Epithelial Mesenchymal Transition ◽  
Resected Specimen ◽  
Mesenchymal Transition ◽  
E Box ◽  
Tumor Transformation ◽  
E Cadherin

Abstract Background The tumor transformation mechanism of a plasmacytoid urothelial carcinoma remains unexplained. We describe the case of a plasmacytoid urothelial carcinoma of the renal pelvis in which the expression of zinc finger E–box–binding homeobox 1 (ZEB1), a key nuclear transcription factor in an epithelial–mesenchymal transition, is involved in tumor transformation. Case presentation The patient had a left nephrectomy with the clinical diagnosis of left pelvic renal cancer. The resected specimen showed that the tumor surface comprised a noninvasive papillary urothelial carcinoma with the carcinoma in situ, and the invasive area comprised a plasmacytoid urothelial carcinoma characterized by the presence of single dyscohesive malignant cells that resembled plasma cells in a loose myxoid stroma. The noninvasive urothelial carcinoma was positive for cytokeratin and E–cadherin, and negative for vimentin and ZEB1. In contrast, the invasive plasmacytoid urothelial carcinoma was positive for cytokeratin and also vimentin and ZEB1, and negative for E–cadherin. Additionally, this component was immunoreactive for CD138 and CD38 that are immunohistochemical markers for plasma cells. Conclusion We suggest that ZEB1 is involved in the plasmacytoid transformation by repressing the E–cadherin in a plasmacytoid urothelial carcinoma.

scholarly journals Expression of epithelial-Mesenchymal transition related markers in Plasmacytoid Urothelial carcinoma of the urinary bladder

BMC Urology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Shunichiro Nomura ◽  
Yasutomo Suzuki ◽  
Jun Akatsuka ◽  
Yuki Endo ◽  
Akira Shimizu ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Urothelial Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals ID1 mediates resistance to osimertinib in EGFR T790M-positive non-small cell lung cancer through epithelial–mesenchymal transition

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kejun Liu ◽  
Xianwen Chen ◽  
Ligang Wu ◽  
Shiyuan Chen ◽  
Nianxin Fang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Small Cell Lung Cancer ◽  
Cell Line ◽  
Epithelial Mesenchymal Transition ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition ◽  
Egfr T790m ◽  
E Cadherin

Abstract Background ID1 is associated with resistance to the first generation of EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC). However, the effect of ID1 expression on osimertinib resistance in EGFR T790M-positive NSCLC is not clear. Methods We established a drug-resistant cell line, H1975/OR, from the osimertinib-sensitive cell line H1975. Alterations in ID1 protein expression and Epithelial–mesenchymal transition (EMT)-related proteins were detected with western blot analysis. RT-PCR was used to evaluate the differences of gene mRNA levels. ID1 silencing and overexpression were used to investigate the effects of related gene on osimertinib resistance. Cell Counting Kit-8 (CCK8) was used to assess the proliferation rate in cells with altered of ID1 expression. Transwell assay was used to evaluate the invasion ability of different cells. The effects on the cell cycle and apoptosis were also compared using flow cytometry. Results In our study, we found that in osimertinib-resistant NSCLC cells, the expression level of the EMT-related protein E-cadherin was lower than that of sensitive cells, while the expression level of ID1 and vimentin were higher than those of sensitive cells. ID1 expression levels was closely related to E-cadherin and vimentin in both osimertinib-sensitive and resistant cells. Alteration of ID1 expression in H1975/OR cells could change the expression of E-cadherin. Downregulating ID1 expression in H1975/OR cells could inhibit cell proliferation, reduce cell invasion, promote cell apoptosis and arrested the cell cycle in the G1/G0 stage phase. Our study suggests that ID1 may induce EMT in EGFR T790M-positive NSCLC, which mediates drug resistance of osimertinib. Conclusions Our study revealed the mechanism of ID1 mediated resistance to osimertinib in EGFR T790M-positive NSCLC through EMT, which may provide new ideas and methods for the treatment of EGFR mutated NSCLC after osimertinib resistance.

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