The role of cell cycle regulatory protein p53 in Follicular neoplasms of thyroid with hurthle cells

Background: The disease biology of Follicular neoplasms of thyroid with hurthle cells is poorly understood. Very few studies in literature have addressed the role of p53 in these neoplasms. The aim of the present study is to analyze the histomorphological features of Follicular neoplasms with hurthle cell change and to evaluate the role of p53 in their tumor biology.Methods:32 cases of Follicular neoplasms of thyroid with focal and pure hurthle cell change over a period of 2.5 years were studied histologically and immunohistochemically using p53 antibody (Biogenex). They included 20 follicular adenomas with focal hurthle cells, 10 pure hurthle cell adenomas and 2 hurthle cell carcinomas.Results: All cases showed nuclear p53 positivity in hurthle cells. Muller-Hocker et al criteria was used for frequency scoring. Out of the 32 cases, 12 cases of pure hurthle cells showed score 3, Remaining 20 cases of follicular adenomas with focal hurthle cell change showed score 3 in cases with >50% hurthle cells, score 2 in cases with 20-40% hurthle cells and score 0 in cases with <10% hurthle cells.Conclusions:The study showed a good correlation of p53 protein expression with tumor progression and aggressiveness. Hence this indicates that molecular alterations in p53 pathway play a role in tumor biology in Follicular neoplasms of thyroid with hurthle cell change.

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Cytotechnologist Performance for Screening Hürthle Cell Atypia in Indeterminate Thyroid Fine-Needle Aspirates

Acta Cytologica ◽

10.1159/000441939 ◽

2015 ◽

Vol 59 (5) ◽

pp. 377-383 ◽

Cited By ~ 1

Author(s):

Christopher J. VandenBussche ◽

Christina Adams ◽

Syed Z. Ali ◽

Matthew T. Olson

Keyword(s):

Diagnostic Errors ◽

Needle Aspiration ◽

Fine Needle ◽

Fine Needle Aspirates ◽

Hürthle Cell ◽

Thyroid Fine Needle Aspiration ◽

Hurthle Cells ◽

Hürthle Cells ◽

Almost All ◽

Cell Atypia

Objectives: We have previously shown that specimens diagnosed as containing Hürthle cells have a 12% chance of being malignant if they are classified as atypia of undetermined significance (AUS-HC). The identification of Hürthle cells by cytotechnologists (CTs) during screening can improve cytopathologist efficiency and may prevent diagnostic errors due to the oversights of focal findings. Here, we examine the performance of our institutional CTs when screening for Hürthle cell atypia in thyroid fine-needle aspiration (FNA) specimens. Study Design: Information on 8,814 thyroid cytopathology specimens was retrieved for a 10-year period. Specimens were screened by 1 of 11 CTs. A subsample of cases was categorized either as AUS-HC or suspicious for Hürthle cell neoplasm. Results: AUS-HC screening diagnoses were more likely to be downgraded to benign but less likely to be upgraded compared to AUS diagnoses with nuclear or microfollicular atypia. AUS-HC represents almost all papillary thyroid carcinoma (PTC) screening diagnoses downgraded to the AUS category, which suggests that even low levels of Hürthle cell atypia can result in PTC being included in the differential diagnosis. Conclusion: Overall, there are few major discrepancies between CT and pathologist diagnoses for specimens containing Hürthle cell atypia.

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Malignancy risk in indeterminate thyroid nodules with Hürthle cells: role of autoimmune thyroiditis

Endocrine ◽

10.1007/s12020-021-02932-6 ◽

2021 ◽

Author(s):

Francesca Perticone ◽

Riccardo Maggiore ◽

Gilberto Mari ◽

Stefano Frara ◽

Paola Baldassarre ◽

...

Keyword(s):

Autoimmune Thyroiditis ◽

Thyroid Nodules ◽

Malignancy Risk ◽

Hurthle Cells ◽

Hürthle Cells

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Constitutive NF-κB maintains high expression of a characteristic gene network, including CD40, CD86, and a set of antiapoptotic genes in Hodgkin/Reed-Sternberg cells

Blood ◽

10.1182/blood.v97.9.2798 ◽

2001 ◽

Vol 97 (9) ◽

pp. 2798-2807 ◽

Cited By ~ 183

Author(s):

Michael Hinz ◽

Peter Löser ◽

Stephan Mathas ◽

Daniel Krappmann ◽

Bernd Dörken ◽

...

Keyword(s):

Gene Network ◽

Target Genes ◽

Dominant Role ◽

Regulatory Protein ◽

Ectopic Expression ◽

Surface Receptors ◽

Antiapoptotic Proteins ◽

Cell Cycle Regulatory Protein ◽

Distinctive Role

Abstract Constitutively activated nuclear factor (NF)-κB is observed in a variety of neoplastic diseases and is a hallmark of the malignant Hodgkin and Reed-Sternberg cells (H/RS) in Hodgkin lymphoma. Given the distinctive role of constitutive NF-κB for H/RS cell viability, NF-κB–dependent target genes were searched for by using adenoviral expression of the super-repressor IκBΔN. A surprisingly small but characteristic set of genes, including the cell-cycle regulatory protein cyclin D2, the antiapoptotic proteins Bfl-1/A1, c-IAP2, TRAF1, and Bcl-xL, and the cell surface receptors CD86 and CD40 were identified. Thus, constitutive NF-κB activity maintains expression of a network of genes, which are known for frequent, marker-like expression in primary or cultured H/RS cells. Intriguingly, CD40, which is able to activate CD86 or Bcl-xL via NF-κB, is itself transcriptionally regulated by NF-κB through a promoter proximal binding site. NF-κB inhibition resulted in massive spontaneous and p53-independent apoptosis, which could be rescued by ectopic expression of Bcl-xL, underscoring its dominant role in survival of H/RS cells. Hence, NF-κB controls a signaling network in H/RS cells, which promotes tumor cell growth and confers resistance to apoptosis.

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The Thyroid Hürthle (Oncocytic) Cell and Its Associated Pathologic Conditions: A Surgical Pathology and Cytopathology Review

Archives of Pathology & Laboratory Medicine ◽

10.5858/2008-132-1241-tthoca ◽

2008 ◽

Vol 132 (8) ◽

pp. 1241-1250 ◽

Cited By ~ 12

Author(s):

Kathleen T. Montone ◽

Zubair W. Baloch ◽

Virginia A. LiVolsi

Keyword(s):

Differential Diagnosis ◽

Medullary Carcinoma ◽

Thyroid Neoplasms ◽

Cell Adenoma ◽

Hürthle Cell ◽

Oncocytic Variant ◽

Hurthle Cells ◽

Hürthle Cells ◽

Thyroid Lesions

Abstract Context.—Hürthle cells are eosinophilic, follicular-derived cells that are associated with a variety of nonneoplastic and neoplastic thyroid lesions. The differential diagnosis of Hürthle cell lesions is quite broad. Objective.—To review the pathologic conditions associated with Hürthle cells in the thyroid and to discuss pathology of thyroid lesions associated with oncocytic cytology. Data Sources.—A variety of thyroid nonneoplastic (autoimmune thyroiditis, multinodular goiter) and neoplastic conditions (Hürthle cell adenoma, Hürthle cell carcinoma) are associated with Hürthle cell cytology. In addition, there are several thyroid neoplasms that should be considered when one observes a Hürthle cell neoplasm in the thyroid (oncocytic variant of medullary carcinoma, several variants of papillary thyroid carcinoma). Conclusions.—Oncocytic cytology is seen in a variety of thyroid conditions that are associated with a broad differential diagnosis and care must be used for accurate diagnosis. Newer molecular-based techniques may be useful for further classification of thyroid neoplasms with oncocytic pathology.

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Molecular Alterations in Thyroid Cancer: From Bench to Clinical Practice

Genes ◽

10.3390/genes10090709 ◽

2019 ◽

Vol 10 (9) ◽

pp. 709 ◽

Cited By ~ 12

Author(s):

Elena Tirrò ◽

Federica Martorana ◽

Chiara Romano ◽

Silvia Rita Vitale ◽

Gianmarco Motta ◽

...

Keyword(s):

Thyroid Cancer ◽

Molecular Mechanisms ◽

Kinase Inhibitors ◽

Tumor Biology ◽

Cancer Development ◽

Disease Evolution ◽

Molecular Alterations ◽

Genomic Landscape ◽

Thyroid Malignancies

Thyroid cancer comprises different clinical and histological entities. Whereas differentiated (DTCs) malignancies are sensitive to radioiodine therapy, anaplastic (ATCs) and medullary (MTCs) tumors do not uptake radioactive iodine and display aggressive features associated with a poor prognosis. Moreover, in a majority of DTCs, disease evolution leads to the progressive loss of iodine sensitivity. Hence, iodine-refractory DTCs, along with ATCs and MTCs, require alternative treatments reflective of their different tumor biology. In the last decade, the molecular mechanisms promoting thyroid cancer development and progression have been extensively studied. This has led to a better understanding of the genomic landscape, displayed by thyroid malignancies, and to the identification of novel therapeutic targets. Indeed, several pharmacological compounds have been developed for iodine-refractory tumors, with four multi-target tyrosine kinase inhibitors already available for DTCs (sorafenib and lenvatinib) and MTCs (cabozantib and vandetanib), and a plethora of drugs currently being evaluated in clinical trials. In this review, we will describe the genomic alterations and biological processes intertwined with thyroid cancer development, also providing a thorough overview of targeted drugs already tested or under investigation for these tumors. Furthermore, given the existing preclinical evidence, we will briefly discuss the potential role of immunotherapy as an additional therapeutic strategy for the treatment of thyroid cancer.

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The Role of Cell Cycle Regulatory Protein, Cyclin D1, in the Progression of Thyroid Cancer

Modern Pathology ◽

10.1038/modpathol.3880157 ◽

2000 ◽

Vol 13 (8) ◽

pp. 882-887 ◽

Cited By ~ 75

Author(s):

Songtao Wang ◽

Ricardo V Lloyd ◽

Michael J Hutzler ◽

Marjorie S Safran ◽

Nilima A Patwardhan ◽

...

Keyword(s):

Cell Cycle ◽

Thyroid Cancer ◽

Cyclin D1 ◽

Regulatory Protein ◽

Cell Cycle Regulatory Protein

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Diagnostic Utility of Intracytoplasmic Lumen and Transgressing Vessels in Evaluation of Hürthle Cell Lesions by Fine-Needle Aspiration

Archives of Pathology & Laboratory Medicine ◽

10.5858/2001-125-1031-duoila ◽

2001 ◽

Vol 125 (8) ◽

pp. 1031-1035 ◽

Cited By ~ 2

Author(s):

Yi J. Yang ◽

Kamal K. Khurana

Keyword(s):

Cell Carcinoma ◽

Hashimoto's Thyroiditis ◽

Cytologic Diagnosis ◽

Fine Needle ◽

Hürthle Cell ◽

Specificity And Sensitivity ◽

Before And After ◽

Hurthle Cells ◽

Hürthle Cells

Abstract Introduction.—Recent abstracts have emphasized the importance of recognizing intracytoplasmic lumen and transgressing vessels as useful criteria enabling distinction between Hürthle cells encountered in neoplastic and nonneoplastic thyroid aspirates. The purpose of this retrospective study was to evaluate if application of these criteria improves specificity and sensitivity of cytologic diagnosis of true Hürthle cell neoplasms. Materials and Methods.—We retrospectively reviewed 30 fine-needle aspirates of thyroid with cytologic diagnosis of Hürthle cell neoplasms (13 cases) and nonneoplastic thyroid with prominent Hürthle cells (17 cases). All cases were evaluated for the presence of intracytoplasmic lumen and transgressing vessels and were reclassified as neoplastic or nonneoplastic based on the presence or absence of 1 or both of these criteria. Surgical follow-up was available in all cases. Results.—Surgical follow-up in 13 cases of Hürthle cell neoplasms revealed Hürthle cell carcinoma (3 cases), Hürthle cell adenoma (6 cases), and Hashimoto's thyroiditis (4 cases). Seventeen cases with nonneoplastic diagnosis revealed Hürthle cell carcinoma (1 case), Hashimoto's thyroiditis (12 cases), and nodular goiter (4 cases). After application of the previously mentioned cytologic criteria, the cytologic diagnoses were reclassified as Hürthle cell neoplasms (13 cases) and nonneoplastic thyroid (17 cases). The true sensitivity of the test before and after the application of the criteria was 90% and 100%, respectively. The true specificity before and after the application of the cytologic criteria was 65% and 85%, respectively. Conclusions.—Intracytoplasmic lumen and transgressing vessels are helpful features in distinguishing neoplastic and nonneoplastic Hürthle cell thyroid lesions. Use of these criteria may improve the specificity and sensitivity of the cytologic diagnosis.

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