scholarly journals MiRNA Deregulation Distinguishes Anaplastic Thyroid Carcinoma (ATC) and Supports Upregulation of Oncogene Expression

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5913
Author(s):  
Danny Misiak ◽  
Marcus Bauer ◽  
Jana Lange ◽  
Jacob Haase ◽  
Juliane Braun ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Neck Region ◽  
Anaplastic Thyroid Carcinoma ◽  
Diagnostic Tools ◽  
Analysis Pipeline ◽  
Head And Neck Region ◽  
Thyroid Carcinomas ◽  
Bona Fide ◽  
Poorly Differentiated ◽  
Mirna Deregulation

Anaplastic thyroid carcinoma (ATC) is the most fatal and rapidly evolving endocrine malignancy invading the head and neck region and accounts for up to 50% of thyroid cancer-associated deaths. Deregulation of the microRNA (miRNA) expression promotes thyroid carcinoma progression by modulating the reorganization of the ATC transcriptome. Here, we applied comparative miRNA–mRNA sequencing on a cohort of 28 thyroid carcinomas to unravel the association of deregulated miRNA and mRNA expression. This identified 85 miRNAs significantly deregulated in ATC. By establishing a new analysis pipeline, we unraveled 85 prime miRNA–mRNA interactions supporting the downregulation of candidate tumor suppressors and the upregulation of bona fide oncogenes such as survivin (BIRC5) in ATC. This miRNA-dependent reprogramming of the ATC transcriptome provided an mRNA signature comprising 65 genes sharply distinguishing ATC from other thyroid carcinomas. The validation of the deregulated protein expression in an independent thyroid carcinoma cohort demonstrates that miRNA-dependent oncogenes comprised in this signature, the transferrin receptor TFRC (CD71) and the E3-ubiquitin ligase DTL, are sharply upregulated in ATC. This upregulation is sufficient to distinguish ATC even from poorly differentiated thyroid carcinomas (PDTC). In sum, these findings provide new diagnostic tools and a robust resource to explore the key miRNA–mRNA regulation underlying the progression of thyroid carcinoma.

scholarly journals Undifferentiated Malignant Neoplasm Involving Parotid and Thyroid: Sampling and PAX8 Cross-Reactivity Can Obscure the Diagnosis of Lymphoma

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Elizabeth W. Hubbard ◽  
Laurentia Nodit ◽  
Stuart Van Meter
Keyword(s):  
Malignant Neoplasm ◽  
Neck Region ◽  
B Cell Lymphoma ◽  
Cross Reactivity ◽  
Anaplastic Thyroid Carcinoma ◽  
Head And Neck Region ◽  
Large B Cell Lymphoma ◽  
Poorly Differentiated ◽  
Malignant Neoplasia ◽  
Selection Of

Poorly differentiated malignant neoplasia arising within the head and neck region may originate from diverse sources. We report a case of a cytologically undifferentiated malignant neoplasm clinically presenting as masses involving thyroid and parotid. Although PAX8 was immunoreactive and thus worrisome for anaplastic thyroid carcinoma, the tumor was eventually proven to represent PAX5 positive diffuse large B-cell lymphoma expressing cross-reactivity with polyclonal PAX8 antibody. Cross-reactivity between commercially available polyclonal PAX8 and PAX5 immunostains has been described in the literature but is not widely known, and it is a potential pitfall for making a misdiagnosis. This distinction can have importance in selection of subsequent clinical therapy and should be considered in choice of immunohistochemical stains for diagnostic purposes.

scholarly journals Etiopathogenesis of Differentiated Thyroid Carcinomas

2016 ◽  
Vol 4 (3) ◽  
pp. 517-522
Author(s):  
Tanja Makazlieva ◽  
Olivija Vaskova ◽  
Venjamin Majstorov
Keyword(s):  
Thyroid Carcinoma ◽  
Epidemiological Studies ◽  
Genetic Alterations ◽  
Anaplastic Thyroid Carcinoma ◽  
Epigenetic Alterations ◽  
Thyroid Carcinomas ◽  
Etiological Factors ◽  
Appropriate Treatment ◽  
Poorly Differentiated ◽  
Thyroid Malignancies

INTRODUCTION: Thyroid malignomas are a heterogeneous group of neoplasm consisting of most frequent differentiated encountered carcinomas, papillary and follicular thyroid carcinoma, then medullary thyroid carcinoma originating from neuroendocrine calcitonin-producing C-cells and rare forms of thyroid lymphomas arising from intrathyroidal lymphatic tissue, thyroid sarcomas and poorly differentiated anaplastic thyroid carcinoma. There are increasing numbers of epidemiological studies and publications that have suggested increased incidence rate of thyroid carcinomas. We have read, analysed and compare available reviews and original articles investigating different etiological factors in the development of thyroid carcinomas through Google Scholar and PubMed Database.DISCUSSION: Aetiology involved in the development of thyroid carcinomas is multifactorial and includes external influences, as well as constitutional predispositions and genetic etiological factors. The actual effect of environmental and constitutional factors is on promoting genetic and epigenetic alterations which result in cell proliferation and oncogenesis. Until now are identified numerous genetic alterations, assumed to have an important role in oncogenesis, with MAPK and PI3K-AKT as crucial signalling networks regulating growth, proliferation, differentiation and cell survival/apoptosis. CONCLUSION: This new molecular insight could have a crucial impact on diagnosis and also on improving and selecting an appropriate treatment to the patients with thyroid malignancies.

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.

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.

Pediatric Angiosarcoma of Soft Tissue: A Rare Clinicopathologic Entity

2010 ◽  
Vol 134 (3) ◽  
pp. 481-485 ◽  
Author(s):  
Lobna Ayadi ◽  
Abdelmajid Khabir
Keyword(s):  
Spindle Cell ◽  
Immunohistochemical Study ◽  
Kaposi Sarcoma ◽  
Neck Region ◽  
Epithelioid Hemangioendothelioma ◽  
Vascular Tumors ◽  
Clinical Settings ◽  
Vascular Differentiation ◽  
Head And Neck Region ◽  
Poorly Differentiated

Abstract Angiosarcomas are rare tumors that predominantly affect adults and elderly patients. Although angiosarcomas are well described in a variety of clinical settings, they have been poorly studied in children and little is known about their biology, natural history, or optimal treatment. Childhood angiosarcomas are exceedingly rare. The head and neck region and mediastinum seem to be the preferred locations. Most tumors are high-grade tumors. Vasoformative architecture is not always obvious on light microscopy requiring the benefit of immunohistochemical study. The differential diagnosis includes Kaposi sarcoma, epithelioid hemangioendothelioma, hemangiopericytoma, and spindle cell hemangioendothelioma whose prognosis is different. Complete resection is required for patients with localized tumors. Malignant vascular tumors are rare in children in the first 2 decades of life and when they do occur they seem to be more aggressive than in adults. Pathologic diagnosis is difficult particularly in poorly differentiated angiosarcomas requiring immunohistochemical study to confirm vascular differentiation.

Problems and Controversies in the Histopathology of Thyroid Carcinomas of Follicular Cell Origin

2009 ◽  
Vol 133 (5) ◽  
pp. 683-691
Author(s):  
Ronald Ghossein
Keyword(s):  
Thyroid Carcinoma ◽  
English Language ◽  
Follicular Carcinoma ◽  
Molecular Data ◽  
Follicular Cell ◽  
Clinical Value ◽  
Thyroid Carcinomas ◽  
Poorly Differentiated ◽  
Disease Entities

Abstract Context.—Despite past and recent efforts, many problems and controversies remain in the classification of thyroid carcinomas of follicular cell origin. These controversies have an impact on the prognosis and therapy of patients with thyroid carcinoma as well as on the development of robust cutting-edge research aimed at better outcome and quality of life. Objective.—To focus on 3 contentious areas with significant clinical value: the follicular variant of papillary thyroid carcinoma, the extent of invasion in follicular carcinoma, and the poorly differentiated thyroid carcinomas. Data Sources.—The published English language literature was reviewed. Conclusions.—Recent data show that prognosis and therapy for many disease entities can be better delineated if a meticulous microscopic examination is performed. An accurate assessment of the extent of invasion (especially vascular) is crucial. Proliferative grading (ie, mitosis and necrosis) is of high prognostic value and should be looked for in every specimen. In addition, molecular data gathered to date can help reassess these tumors at the histologic level. Classification proposals based on personal experience rather than adequate and careful clinical follow-up should be discouraged.

scholarly journals Virotherapy as a Potential Therapeutic Approach for the Treatment of Aggressive Thyroid Cancer

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1532 ◽  
Author(s):  
Malfitano ◽  
Somma ◽  
Prevete ◽  
Portella
Keyword(s):  
Thyroid Carcinoma ◽  
Therapeutic Potential ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Differentiated Thyroid Carcinoma ◽  
Anaplastic Thyroid Carcinoma ◽  
Oncolytic Viruses ◽  
Cancer Models ◽  
Poorly Differentiated ◽  
Immunosuppressive Microenvironment

Virotherapy is a novel cancer treatment based on oncolytic viruses (OVs), which selectively infect and lyse cancer cells, without harming normal cells or tissues. Several viruses, either naturally occurring or developed through genetic engineering, are currently under investigation in clinical studies. Emerging reports suggesting the immune-stimulatory property of OVs against tumor cells further support the clinical use of OVs for the treatment of lesions lacking effective therapies. Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC), have a poor prognosis and limited treatment options. Therefore, several groups investigated the therapeutic potential of OVs in PDTC/ATC models producing experimental data sustaining the potential clinical efficacy of OVs in these cancer models. Moreover, the presence of an immunosuppressive microenvironment further supports the potential use of OVs in ATC. In this review, we present the results of the studies evaluating the efficacy of OVs alone or in combination with other treatment options. In particular, their potential therapeutic combination with multiple kinases inhibitors (MKIs) or immune checkpoint inhibitors are discussed.

scholarly journals Sentinel Node Detection in Head and Neck Malignancies: Innovations in Radioguided Surgery

2009 ◽  
Vol 2009 ◽  
pp. 1-10 ◽  
Author(s):  
L. Vermeeren ◽  
W. M. C. Klop ◽  
M. W. M. van den Brekel ◽  
A. J. M. Balm ◽  
O. E. Nieweg ◽  
...  
Keyword(s):  
Sentinel Node ◽  
Head And Neck ◽  
Scientific Progress ◽  
Neck Region ◽  
Diagnostic Tools ◽  
Lymph Node Status ◽  
Radioguided Surgery ◽  
Sentinel Node Detection ◽  
Head And Neck Region ◽  
Sentinel Nodes

Sentinel node mapping is becoming a routine procedure for staging of various malignancies, because it can determine lymph node status more precisely. Due to anatomical problems, localizing sentinel nodes in the head and neck region on the basis of conventional images can be difficult. New diagnostic tools can provide better visualization of sentinel nodes. In an attempt to keep up with possible scientific progress, this article reviews new and innovative tools for sentinel node localization in this specific area. The overview comprises a short introduction of the sentinel node procedure as well as indications in the head and neck region. Then the results of SPECT/CT for sentinel node detection are described. Finally, a portable gamma camera to enable intraoperative real-time imaging with improved sentinel node detection is described.

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