Evaluation of E-Cadherin and β-Catenin Immunoreactivity for Determining Undifferentiated Cells in Anaplastic Thyroid Carcinoma

Pathobiology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Risa Kanematsu ◽  
Mitsuyoshi Hirokawa ◽  
Aki Tanaka ◽  
Ayana Suzuki ◽  
Miyoko Higuchi ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Thyroid Carcinoma ◽  
Undifferentiated Carcinoma ◽  
Anaplastic Thyroid Carcinoma ◽  
Carcinoma Cells ◽  
Membrane Expression ◽  
Thyroid Carcinomas ◽  
Nuclear Expression ◽  
Thyroid Transcription Factor 1 ◽  
E Cadherin

<b><i>Introduction:</i></b> An immunohistochemical study has occasionally been performed to diagnose anaplastic thyroid carcinoma (ATC). However, antibodies to confirm the undifferentiated nature of ATC have not yet been evaluated. The aim of this study was to evaluate E-cadherin and β-catenin expressions in immunoreactivity to determine undifferentiated carcinoma cells in the diagnosis of ATC. <b><i>Methods:</i></b> We immunohistochemically examined 29 ATCs, 30 poorly differentiated thyroid carcinomas (PDTCs), 22 well-differentiated thyroid carcinomas (WDTCs), and 3 squamous cell carcinomas. Antibodies for thyroid transcription factor-1 (TTF-1), paired-box gene 8 (PAX8), β-catenin, and E-cadherin were used. <b><i>Results:</i></b> All WDTCs tested positive for TTF-1, PAX8, and E-cadherin. The positive rates of TTF-1, PAX8, and E-cadherin were 93.3, 93.3, and 100%, respectively, in PDTCs and 17.2, 51.7, and 10.3%, respectively, in ATCs. WDTC expressed the lateral cell membrane staining for β-catenin and E-cadherin, whereas PDTC showed circumferential cell membranous expression (fishnet pattern). β-catenin cell membrane expression in ATCs is lost or discontinuous. Carcinoma cells with β-catenin nuclear expression without cell membranous expression were scattered in 72.4% of ATCs but were not observed in the other carcinomas. <b><i>Conclusion:</i></b> We propose 3 immunohistochemical findings to determine undifferentiated carcinoma cells in the diagnosis of ATC: (1) β-catenin nuclear expression with no or reduced cell membranous expression, (2) the loss or discontinuous pattern of E-cadherin expression, and (3) the loss of PAX8 nuclear expression.

Interactions of Vascular Endothelial Growth Factor and p53 with miR-195 in Thyroid Carcinoma: Possible Therapeutic Targets in Aggressive Thyroid Cancers

2019 ◽  
Vol 19 (7) ◽  
pp. 561-570 ◽  
Author(s):  
Hamidreza Maroof ◽  
Soussan Irani ◽  
Armin Arianna ◽  
Jelena Vider ◽  
Vinod Gopalan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thyroid Carcinoma ◽  
Cell Cycle Progression ◽  
P53 Protein ◽  
Carcinoma Cells ◽  
Vascular Endothelial ◽  
Papillary Thyroid ◽  
Cycle Progression ◽  
Thyroid Carcinomas ◽  
Endothelial Growth Factor

Background: The clinical pathological features, as well as the cellular mechanisms of miR-195, have not been investigated in thyroid carcinoma. Objective: The aim of this study is to identify the interactions of vascular endothelial growth factor (VEGF), p53 and miR-195 in thyroid carcinoma. The clinical and pathological features of miR-195 were also investigated. Methods: The expression levels of miR-195 were identified in 123 primary thyroid carcinomas, 40 lymph nodes with metastatic papillary thyroid carcinomas and seven non-neoplastic thyroid tissues (controls) as well as two thyroid carcinoma cell lines, B-CPAP (from metastasizing human papillary thyroid carcinoma) and MB-1 (from anaplastic thyroid carcinoma), by the real-time polymerase chain reaction. Using Western blot and immunofluorescence, the effects of exogenous miR-195 on VEGF-A and p53 protein expression levels were examined. Then, cell cycle and apoptosis assays were performed to evaluate the roles of miR-195 in cell cycle progression and apoptosis. Results: The expression of miR-195 was downregulated in majority of the papillary thyroid carcinoma tissue as well as in cells. Introduction of exogenous miR-195 resulted in downregulation of VEGF-A and upregulation of p53 protein expressions. Upregulation of miR-195 in thyroid carcinoma cells resulted in cell cycle arrest. Moreover, we demonstrated that miR-195 inhibits cell cycle progression by induction of apoptosis in the thyroid carcinoma cells. Conclusion: Our findings showed for the first time that miR-195 acts as a tumour suppressor and regulates cell cycle progression and apoptosis by targeting VEGF-A and p53 in thyroid carcinoma. The current study exhibited that miR-195 might represent a potential therapeutic target for patients with thyroid carcinomas having aggressive clinical behaviour.

scholarly journals Enhancer of Zeste Homolog 2 Overexpression Has a Role in the Development of Anaplastic Thyroid Carcinomas

2011 ◽  
Vol 96 (4) ◽  
pp. 1029-1038 ◽  
Author(s):  
Eleonora Borbone ◽  
Giancarlo Troncone ◽  
Angelo Ferraro ◽  
Zuzana Jasencakova ◽  
Lovorka Stojic ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Anaplastic Thyroid Carcinoma ◽  
Polycomb Group ◽  
Migration And Invasion ◽  
Polycomb Group Protein ◽  
Expression Levels ◽  
Thyroid Carcinomas ◽  
Enhancer Of Zeste ◽  
Pax8 Gene ◽  
Group Protein

Abstract Context: Enhancer of zeste homolog 2 (EZH2) is a histone lysine methyltransferase belonging to the polycomb group protein family. Overexpression of EZH2 has been found in several human malignancies including hematological and solid tumors. Objectives: In this study we investigated the expression levels of EZH2 and its polycomb group protein partners in thyroid carcinoma tissues with different degrees of malignancy to identify potential new therapeutic targets for anaplastic thyroid carcinoma (ATC). Results: We show that high EZH2 expression levels are characteristic of undifferentiated ATC, whereas no significant changes were observed in well-differentiated papillary and follicular thyroid carcinomas as compared with normal thyroid. Knockdown of EZH2 in ATC cell lines results in cell growth inhibition, loss of anchorage-independent growth, migration, and invasion properties. Moreover, we demonstrate that EZH2 directly controls differentiation of ATC cells by silencing the thyroid specific transcription factor paired-box gene 8 (PAX8). Conclusions: EZH2 is specifically overexpressed in ATC, and it directly contributes to transcriptional silencing of PAX8 gene and ATC differentiation.

scholarly journals Thyroid Transcription Factor � 1 (TTF-1) Immunoexpression in Thyroid Carcinoma with Follicular Origin

2001 ◽  
Vol 71 (3) ◽  
pp. 185-191
Author(s):  
Amadeus Dobrescu ◽  
Cristi Tarta ◽  
Marioara Cornianu ◽  
Codruta Lazureanu ◽  
Ioana Golu ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Recurrent Disease ◽  
Clinical Behavior ◽  
Thyroid Carcinomas ◽  
Nuclear Expression ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Transcription Factor 1 ◽  
Benign Thyroid ◽  
Thyroid Lesions

Differentiated thyroid carcinomas are heterogeneous diseases with clinical and morphological features insufficient to predict their clinical behavior. The expression of tissue-specific transcription factors that control differentiated phenotype can be an additional method in evaluating the aggressiveness of a tumor, when differentiation markers and malignant phenotype of tumor cells are inconclusive. The expression of thyroid transcription factor-1 (TTF-1) is limited to thyroid follicular cells; it is a nuclear protein expressed in the epithelial cells of the thyroid, lungs and diencephalon. Using the monoclonal mouse antibody, clone 8G7G3/1, we examined the immunohistochemical expression of TTF-1 protein in 26 thyroid carcinomas (22 papillary carcinomas � PTC, 2 follicular carcinomas � FTC, 2 anaplastic carcinomas - AC), 4 follicular adenomas � FA, 10 benign thyroid lesions as underlying diseases (multinodular goiter � 3, Hashimoto thyroiditis � 3, Graves Basedow disease - 4) and sections of normal thyroid tissue, assessing the possible correlations with clinical and morphological features, as well as patient outcomes.TTF-1 nuclear expression was identified in 75% of benign thyroid lesions and 18/26 (69.23%) carcinomas. We noted TTF-1 nuclear expression in 68.18% of PTC (10% being associated with recurrent disease) and the absence of immunoreaction in 31.82% of PTC without recurrent disease. In patients with PTC, the risk of recurrence was significantly associated with the presence of nuclear TTF-1 expression in the primary tumor (p[0.001), but was not influenced by the type of surgery performed (p]0.05) or patients� age. TTF-1 nuclear expression did not correlate with patients� gender, tumor size, extent of disease at the moment of diagnosis and multifocal tumors (p]0.05). TTF-1 nuclear reactivity can be elevated in differentiated thyroid tumors (PTC and FTC) with aggressive clinical behavior that will develop recurrent or persistent disease. In anaplastic thyroid carcinomas with fast growth rate, immunoreactivity for TTF-1 and Ki-67 can offer useful information for tumor cell differentiation, while in the case of a mixed thyroid tumor it helps in distinguishing between well differentiated and undifferentiated/anaplastic areas.

scholarly journals Imatinib enhances docetaxel-induced apoptosis through inhibition of nuclear factor-κB activation in anaplastic thyroid carcinoma cells

Thyroid ◽  
2012 ◽  
pp. 120406132503004
Author(s):  
EunSook Kim ◽  
Michiko Matsuse ◽  
Vladimir Saenko ◽  
Keiji Suzuki ◽  
Akira Ohtsuru ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Nuclear Factor Κb ◽  
Anaplastic Thyroid Carcinoma ◽  
Carcinoma Cells ◽  
Nuclear Factor ◽  
Induced Apoptosis

scholarly journals Anoctamin-1 affects the migration and invasion of anaplastic thyroid carcinoma cells

2019 ◽  
Vol 23 (4) ◽  
pp. 294-301 ◽  
Author(s):  
Jae-Young Kim ◽  
Hwa Young Youn ◽  
June Choi ◽  
Seung Kuk Baek ◽  
Soon Young Kwon ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Anaplastic Thyroid Carcinoma ◽  
Carcinoma Cells ◽  
Migration And Invasion ◽  
Anoctamin 1

scholarly journals Differential roles of RET isoforms in medullary and papillary thyroid carcinomas

2017 ◽  
Vol 24 (1) ◽  
pp. 53-69 ◽  
Author(s):  
Eric Y Lian ◽  
Sarah M Maritan ◽  
Jessica G Cockburn ◽  
Katayoon Kasaian ◽  
Mathieu J F Crupi ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Cell Survival ◽  
Tumour Progression ◽  
Carcinoma Cells ◽  
Protein Isoforms ◽  
Human Thyroid ◽  
Papillary Thyroid ◽  
Anoikis Resistance ◽  
Thyroid Carcinomas ◽  
And Migration

The RET receptor tyrosine kinase mediates cell proliferation, survival and migration in embryogenesis and is implicated in the transformation and tumour progression in multiple cancers. RET is frequently mutated and constitutively activated in familial and sporadic thyroid carcinomas. As a result of alternative splicing, RET is expressed as two protein isoforms, RET9 and RET51, which differ in their unique C-terminal amino acids. These isoforms have distinct intracellular trafficking and associated signalling complexes, but functional differences are not well defined. We used shRNA-mediated knockdown (KD) of individual RET isoforms or of total RET to evaluate their functional contributions in thyroid carcinoma cells. We showed that RET is required for cell survival in medullary (MTC) but not papillary thyroid carcinoma (PTC) cells. In PTC cells, RET depletion reduced cell migration and induced a flattened epithelial-like morphology. RET KD decreased the expression of mesenchymal markers and matrix metalloproteinases and reduced anoikis resistance and invasive potential. Further, we showed that RET51 depletion had significantly greater effects on each of these processes than RET9 depletion in both MTC and PTC cells. Finally, we showed that expression of RET, particularly RET51, was correlated with malignancy in a panel of human thyroid tumour tissues. Together, our data show that RET expression promotes a more mesenchymal phenotype with reduced cell–cell adhesion and increased invasiveness in PTC cell models, but is more important for tumour cell survival, proliferation and anoikis resistance in MTC models. Our data suggest that the RET51 isoform plays a more prominent role in mediating these processes compared to RET9.

scholarly journals C6-ceramide Inhibits the Motility of Anaplastic Thyroid Carcinoma Cells

2020 ◽  
Vol 63 (2) ◽  
pp. 95-98
Author(s):  
Kazunori Fujiwara ◽  
Hiroaki Yazama ◽  
Ryohei Donishi ◽  
Satoshi Koyama ◽  
Takahiro Fukuhara ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Anaplastic Thyroid Carcinoma ◽  
Carcinoma Cells
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