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

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.

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

Diagnostic Pathology ◽

10.1186/s13000-020-01043-6 ◽

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.

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Form follows function: Morphological and immunohistological insights into epithelial–mesenchymal transition characteristics of tumor buds

Tumor Biology ◽

10.1177/1010428317705501 ◽

2017 ◽

Vol 39 (5) ◽

pp. 101042831770550 ◽

Cited By ~ 9

Author(s):

Kathrin Enderle-Ammour ◽

Moritz Bader ◽

Theresa Dorothee Ahrens ◽

Kai Franke ◽

Sylvia Timme ◽

...

Keyword(s):

Tumor Cell ◽

Zinc Finger ◽

Cell Morphology ◽

Epithelial Mesenchymal Transition ◽

Three Dimensional ◽

Tumor Budding ◽

Mesenchymal Transition ◽

Tumor Mass ◽

E Box ◽

E Cadherin

In cancer biology, the architectural concept “form follows function” is reflected by cell morphology, migration, and epithelial–mesenchymal transition protein pattern. In vivo, features of epithelial–mesenchymal transition have been associated with tumor budding, which correlates significantly with patient outcome. Hereby, the majority of tumor buds are not truly detached but still connected to a major tumor mass. For detailed insights into the different tumor bud types and the process of tumor budding, we quantified tumor cells according to histomorphological and immunohistological epithelial–mesenchymal transition characteristics. Three-dimensional reconstruction from adenocarcinomas (pancreatic, colorectal, lung, and ductal breast cancers) was performed as published. Tumor cell morphology and epithelial–mesenchymal transition characteristics (represented by zinc finger E-box-binding homeobox 1 and E-Cadherin) were analyzed qualitatively and quantitatively in a three-dimensional context. Tumor buds were classified into main tumor mass, connected tumor bud, and isolated tumor bud. Cell morphology and epithelial–mesenchymal transition marker expression were assessed for each tumor cell. Epithelial–mesenchymal transition characteristics between isolated tumor bud and connected tumor bud demonstrated no significant differences or trends. Tumor cell count correlated significantly with epithelial–mesenchymal transition and histomorphological characteristics. Regression curve analysis revealed initially a loss of membranous E-Cadherin, followed by expression of cytoplasmic E-Cadherin and subsequent expression of nuclear zinc finger E-box-binding homeobox 1. Morphologic changes followed later in this sequence. Our data demonstrate that connected and isolated tumor buds are equal concerning immunohistochemical epithelial–mesenchymal transition characteristics and histomorphology. Our data also give an insight in the process of tumor budding. While there is a notion that the epithelial–mesenchymal transition zinc finger E-box-binding homeobox 1–E-Cadherin cascade is initiated by zinc finger E-box-binding homeobox 1, our results are contrary and outline other possible pathways influencing the regulation of E-Cadherin.

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Zinc finger E-box-binding homeobox 1 (ZEB1): A novel predictor for the prognosis in gastrointestinal tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e23515 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e23515-e23515

Author(s):

Shenglan Yang ◽

Jiang Min

Keyword(s):

Zinc Finger ◽

Epithelial Mesenchymal Transition ◽

High Expression ◽

Mesenchymal Transition ◽

Cancer Breast ◽

Female Rate ◽

Significant Difference ◽

E Box ◽

Progression Of Disease ◽

Low Expression

e23515 Background: The gastrointestinal stromal tumors (GISTs) are the most common soft tissue sarcoma arising anywhere along gastrointestinal tract. The advanced and metastatic GISTs are the leading cause in GISTs inducing death. GISTs are the most commonly resulted from KIT or PDGFRA activation mutation. Currently adjuvant therapy with imatinib also targets the KIT and PDGFRA signals, which significantly increases the relapse-free survival and overall survival. However, KIT and PDGFRA mutation are not completely responsible for the progression of disease, especially metastasis of GISTs. So, there could be other molecular mechanism in GISTs progression. ZEB1 (zinc finger E-box-binding homeobox 1), as a member in zinc finger and homeodomain transcriptional factor family, plays a key role in metastasis of some epithelial carcinomas, such as colorectal cancer, breast cancer and NSCLC. We present that ZEB1, as a vital molecular in epithelial-mesenchymal transition, could be a promising marker in predicting the prognosis in GISTs. Methods: Immunohistochemistry staining for paraffin-embedding slices from 157 patients firstly diagnosed as GIST is applied for detecting the ZEB1 expression. Clinical, pathological, molecular and survival time were analyzed. All performances were approved by the Medical Ethics Committee in the First Affiliated Hospital of Chongqing Medical University. Results: In 157 patients, metastasis was found in 87 patients. In 87 patients with metastasis, high expression of ZEB1 almost exhibited (80 high/96 VS 7 non or low/96), while non or low expression was frequently detected in patients without metastasis (50 non or low/70 VS 20 high/70) (p < 0.0001). There was no significant difference between high and non/low expression patients in gender (48% VS 46% for male rate; 52% VS 54% for female rate), age (53 vs 54 years for median age), primary location (esophagus 2% VS 1.8%; stomach 57% VS 52.6%; duodenum and small intestine 31% VS 31.6%; colorectum and anus 10% VS 14.0%), tumor size (0.5-24cm, median 9.7cm VS 1-25.5cm, median 10.1cm), mitotic index (55.0% VS 58.6% for > 5/50HPF; 45.0% VS 41.4% for ≤5/50HPF), and risk stratification (low/intermediate risk 60.7% VS 63%; high risk 39.3% VS 37%). In addition, the 5-year OS rate was considerably lower in patients with ZEB1 high expression than those with ZEB1 none or low expression at baseline (37% vs 86%; p = 0.011). Conclusions: High expression of ZEB1 facilitates metastasis and indicates the poor prognosis in GISTs. ZEB1 could be a novel predictor for GIST’s prognosis.

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Prognostic significance of the epithelial-mesenchymal transition factor zinc finger E-box-binding homeobox 2 in esophageal squamous cell carcinoma

Oncology Letters ◽

10.3892/ol.2017.6559 ◽

2017 ◽

Vol 14 (3) ◽

pp. 2683-2690 ◽

Cited By ~ 3

Author(s):

Xiaodong Huo ◽

Bin Huo ◽

Huixing Wang ◽

Hongdian Zhang ◽

Zhao Ma ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Zinc Finger ◽

Squamous Cell ◽

Epithelial Mesenchymal Transition ◽

Prognostic Significance ◽

Mesenchymal Transition ◽

E Box

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

10.21203/rs.2.21996/v1 ◽

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.

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Sa1787 Regulation of Chemotherapy Resistance Through Epithelial-Mesenchymal Transition by Zinc Finger E-Box-Binding Proteins

Gastroenterology ◽

10.1016/s0016-5085(12)61224-4 ◽

2012 ◽

Vol 142 (5) ◽

pp. S-326

Author(s):

Shinya Ohashi ◽

Seiji Naganuma ◽

Mitsuteru Natsuizaka ◽

Shingo Kagawa ◽

Hideaki Kinugasa ◽

...

Keyword(s):

Zinc Finger ◽

Binding Proteins ◽

Epithelial Mesenchymal Transition ◽

Chemotherapy Resistance ◽

Mesenchymal Transition ◽

E Box

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

10.21203/rs.2.21996/v3 ◽

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.

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Regulation of E-cadherin

Breast Cancer Online ◽

10.1017/s1470903105003159 ◽

2005 ◽

Vol 8 (3) ◽

Cited By ~ 4

Author(s):

Z. Yang ◽

H. Zhang ◽

R. Kumar

Keyword(s):

Transcription Factors ◽

Present Article ◽

Zinc Finger ◽

Molecular Basis ◽

Epithelial Mesenchymal Transition ◽

Major Contributor ◽

Mesenchymal Transition ◽

Snail Family ◽

E Cadherin

Numerous studies suggest that loss of E-cadherin is necessary to induce Epithelial–mesenchymal transition (EMT) and metastasis. Snail is a major contributor to EMTs. The Snail family of zinc-finger transcription factors interact with the E-cadherin promoter to repress transcription during EMT. The present article reviews the regulation of E-cadherin and discusses recent novel insights into the molecular basis in the process of EMT.

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