Modern concepts of the molecular pathogenesis of thyroid cancer

Thyroid cancer remains the most common malignancy of the endocrine system worldwide. The indicators of its morbidity and mortality rates have been increasing rapidly over the last decades. Most cases of differentiated thyroid cancer (follicular and papillary histotypes) are clinically manifested by nodular goiter frequently combined with uncertain results of cytological diagnosis (categories III and IV according to the Bethesda (Bethesda System for Reporting Thyroid Cytopathology) classification). All of that makes it difficult to choose a proper tactic for patient treatment. It is known that the development, progression, invasion, and metastasis of cancer cells are regulated by a variety of molecular mechanisms. This review describes several molecular aspects of thyroid nodules oncogenesis, as well as its most promising diagnostic tumor markers. Following molecular pathways are described in particular: gene mutations, protein tumor markers, and epigenetic effects of micro-RNA, histones, as well as DNA methylation. The study of the pathogenesis of this disease has a prognostic value and contributes to the search for effective therapeutic and diagnostic methods and their improvement. That is why we also reviewed modern test panels aimed at preoperative differential diagnosis of thyroid nodules. Summarizing the results of world research on this topic allows us not only to expand the understanding of the fundamental processes of oncogenesis, but also to outline promising areas for future experimental research projects. All of that together will contribute to developing new prognostic, diagnostic and therapeutic technologies, and as a result, will improve the quality of medical care for patients with thyroid cancer.

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Congenital hypothyroidism and thyroid cancer

Endocrine Related Cancer ◽

10.1530/erc-21-0159 ◽

2021 ◽

Author(s):

Gustavo Penna ◽

Ileana G S Rubio ◽

Ester Saraiva Brust ◽

Juliana Cazarin ◽

Fabio Hecht ◽

...

Keyword(s):

Thyroid Cancer ◽

Congenital Hypothyroidism ◽

Molecular Mechanisms ◽

Gene Mutations ◽

Nodular Goiter ◽

Analytical Framework ◽

Differentiated Thyroid Carcinoma ◽

Thyroid Stimulating Hormone ◽

Driver Mutations ◽

Cellular Mechanisms

Differentiated thyroid carcinoma (DTC) combined whit congenital hypothyroidism (CH) is a rare situation, and there is no well-established causal relationship. CH is a common congenital endocrine, while DTC occurring in childhood represents 0.4% to 3% of all malignancies at this stage of life. The association of CH with DTC could be related to dyshormonogenetic goiter (DHG) or developmental abnormalities. This review will explore the clinical features and the molecular mechanisms potentially associated with the appearance of DTC in CH: sporadic somatic driver mutations, chronic increase of thyroid-stimulating hormone (TSH) levels, higher concentrations hydrogen peroxide (H2O2), Borelain /CDCA8 gene mutations and in others genes associated with CH - either alone or associated with the mechanisms involved in dyshormonogenesis. There are some pitfalls in the diagnosis of thyroid cancer in patients with CH with nodular goiter, as the proper cytological diagnosis of nodules of patients with dyshormonogenesis might be demanding due to the specific architectural and cytological appearance, which may lead to an erroneous interpretation of malignancy. The purpose of this article is to suggest an analytical framework that embraces the fundamental relationships between the various aspects of CH and CDT. In face of this scenario, the entire genetic and epigenetic context, the complex functioning and cross talk of cell signaling may determine cellular mechanisms promoting both the maintenance of the differentiated state of the thyroid follicular cell and the disruption of its homeostasis leading to cancer. Whereas, the exact mechanisms for thyroid cancer development in CH remain to be elucidated.

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The Accuracy of ACR TI-RADS Classification of Neck Ultrasound as a First-Line Diagnostic Approach for Thyroid Neoplasms in Pediatric Patients: A Retrospective Study

Oncopediatrics ◽

10.15690/onco.v5i1.1862 ◽

2018 ◽

Vol 5 (1) ◽

pp. 13-23

Author(s):

Nikolai S. Grachev ◽

Elena V. Feoktistova ◽

Igor N. Vorozhtsov ◽

Natalia V. Babaskina ◽

Ekaterina Yu. Iaremenko ◽

...

Keyword(s):

Thyroid Cancer ◽

Predictive Value ◽

Thyroid Nodules ◽

Pediatric Patients ◽

Thyroid Neoplasms ◽

Diagnostic Methods ◽

Diagnostic Approach ◽

First Line ◽

Neck Ultrasound

Background.Ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) is the gold standard in diagnosing the pathological nature of undetermined thyroid nodules. However, in some instances limitations and shortcomings arise, making it insufficient for determining a specific diagnosis.Objective.Our aim was to evaluate the effectiveness of ACR TI-RADS classification of neck ultrasound as a first-line diagnostic approach for thyroid neoplasms in pediatric patients.Methods.A retrospective analysis was made of FNA and US protocols in 70 patients who underwent the examination and treatment at Dmitry Rogachev National Research Center between January 2012 and August 2017. In the retrospective series 70% (49/70) of patients undergone FNA and 43% (30/70) of them undergone repeated FNA. All US protocols were interpreted according to ACR TI-RADS system by the two independent experts. The clinical judgment was assessed using the concordance test and the reliability of preoperative diagnostic methods was analized.Results.According to histologic examination protocols, benign nodules reported greater multimorbidity 29% (20/70), compared with thyroid cancer 17% (12/70), complicating FNA procedure. A statistically significant predictor of thyroid cancer with a tumor size ACR TI-RADS showed a significant advantage of ACR TI-RADS due to higher sensitivity (97.6 vs 60%), specificity (78.6 vs 53.8%), positive predictive value (87.2 vs 71.4%), and negative predictive value (95.7 vs 41.2%). Concordance on the interpreted US protocols according to ACR TI-RADS classification between two experts was high, excluding accidental coincidence.Conclusion.The data support the feasibility of US corresponding to the ACR TI-RADS classification as a first-line diagnostic approach for thyroid neoplasm reducing the number of unnecessary biopsies for thyroid nodules.

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Clinical features and results of laboratory and instrumental examination of patients with nodular structures in the thyroid gland in real clinical practice

Clinical Medicine (Russian Journal) ◽

10.18821/0023-2149-2017-95-4-355-361 ◽

2017 ◽

Vol 95 (4) ◽

pp. 355-361

Author(s):

I. S. Berezkina ◽

T. V. Saprina ◽

A. P. Zima ◽

A. V. Isaeva ◽

V. N. Latypova ◽

...

Keyword(s):

Thyroid Cancer ◽

Clinical Practice ◽

Thyroid Nodules ◽

Statistical Data ◽

Clinical Laboratory ◽

Nodular Goiter ◽

High Sensitivity ◽

Cancer Research Institute ◽

The City ◽

Malignancy Potential

The ever increasing incidence of thyroid cancer throughout the world poses the problem of differential diagnosis of thyroid nodules at various stages of their formation. Objective: to determine the most important clinical, laboratory and instrumental parameters of thyroid nodules for the assessment of their malignancy potential and to identify "defects" of clinical and instrumental examination of patients with nodular goiter in clinical practice. Materials and methods: we analyzed the data of general clinical research, hormonal profile, and thyroid ultrasound studies performed on the basis of various clinics in the city of Tomsk (41%), Endocrinology Department of the OGAUZ TOKB consultative and diagnostic polyclinic (28 %), and Cancer Research Institute (31%) for the period from 2012 to 2014. The patients were selected for surgery. Pre-operative data were compared with histological features of the nodules. Results: we analyzed «defects» of patient examination, statistical data on clinical and laboratory-instrumental parameters of thyroid nodules. Conclusion: «defects» of description of ultrasound data significantly reduce sensitivity of the method for predicting malignancy of thyroid nodules. The description of the material obtained by US-FNA alone, in the absence of the conclusion of medical cytologists, has no informative value. Low specificity of a cytological study (48.4%) and its high sensitivity (95.8%) suggests overdiagnosis of thyroid cancer.

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Papillary thyroid cancer in an adolescent with a toxic single nodular goiter

Problems of Endocrinology ◽

10.14341/probl2017632114-116 ◽

2017 ◽

Vol 63 (2) ◽

pp. 114-116 ◽

Cited By ~ 1

Author(s):

Olga S. Rogova ◽

Goar F. Okminyan ◽

Lubov N. Samsonova ◽

Elena V. Kiseleva ◽

Oleg Yu. Latyshev ◽

...

Keyword(s):

Thyroid Cancer ◽

Thyroid Nodule ◽

Papillary Thyroid Cancer ◽

Thyroid Nodules ◽

Fine Needle Aspiration Biopsy ◽

Nodular Goiter ◽

Needle Aspiration ◽

Papillary Thyroid ◽

Risk Of Malignancy ◽

Functional Autonomy

The rate of nodular goiter in children ranges from 0.05 to 5.1%; in this case, the risk of thyroid cancer in childhood amounts to 3―70% of all cases of thyroid pathology. Therefore, the main issue is the differential diagnosis of a nosological variant of a thyroid nodule, which defines the optimal therapeutic tactics for a particular patient. The risk of malignancy is traditionally believed to be low in the case of decompensated functional autonomy of a thyroid nodule; therefore, the need for fine needle aspiration biopsy (FNAB) followed by cytomorphological analysis of the aspirate is avoided in most cases. The presented clinical case demonstrates papillary cancer in an adolescent with a toxic single nodular goiter. A thyroid ultrasound examination revealed a nodular lesion in the boy. An increase in the thyroid size and thyrotoxicosis manifestation occurred 3 years later. A cytomorphological study identified follicular neoplasia; scintigraphy revealed a hot nodule. Surgical treatment was planned. Antithyroid therapy was prescribed to prepare for surgery. After compensation of thyrotoxicosis, hemithyroidectomy was performed. A histological examination diagnosed papillary thyroid cancer, which required repeated thyroidectomy followed by radioiodine I131 ablation. The postoperative period was uneventful; the patient well tolerated suppressive levothyroxine therapy. Therefore, the presence of a toxic single nodular goiter does not exclude thyroid cancer, which defines the need to discuss the indications for FNAB of thyroid nodules in children.

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Molecular markers as risk factors for thyroid cancer

Terapevticheskii arkhiv ◽

10.26442/00403660.2019.10.000357 ◽

2019 ◽

Vol 91 (10) ◽

pp. 119-123

Author(s):

M O Rogova ◽

S V Novosad ◽

N S Martirosian ◽

L V Trukhina ◽

N A Petunina

Keyword(s):

Thyroid Cancer ◽

Thyroid Nodules ◽

Malignant Tumors ◽

Molecular Genetic ◽

Endocrine System ◽

Diagnostic Value ◽

Needle Aspiration ◽

Molecular Genetic Testing ◽

Papillary Cancer ◽

The Past

Thyroid cancer is the most common malignant tumor of the endocrine system. An increase in the incidence of thyroid cancer has been noted over the past decade, mainly due to papillary cancer. The influence of environmental factors, increased availability of medical care, including sensitive diagnostic tests, such as ultrasound and fine - needle aspiration (FNA), can affect the fact of the growth of this incidence. Palpation of thyroid gland has very low diagnostic value for detecting thyroid cancer, while thyroid ultrasound and FNA can detect malignant tumors in 20% of cases. Today, the FNA is the fastest, most accurate, economically accessible, and quite safe method for cytological diagnosis of the thyroid nodules. And molecular genetic testing of FNA samples could serve as an additional reliable diagnostic tool in the case of atypia of undetermined significance.

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Thyroid Cancer and Circadian Clock Disruption

Cancers ◽

10.3390/cancers12113109 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3109

Author(s):

Roberta Malaguarnera ◽

Caterina Ledda ◽

Agnese Filippello ◽

Francesco Frasca ◽

Vincenzo Cristian Francavilla ◽

...

Keyword(s):

Insulin Resistance ◽

Thyroid Cancer ◽

Circadian Clock ◽

Sleep Disturbances ◽

Molecular Mechanisms ◽

Clock Genes ◽

Endocrine System ◽

Diagnostic Procedures ◽

Jet Lag ◽

Common Malignancy

Thyroid cancer (TC) represents the most common malignancy of the endocrine system, with an increased incidence across continents attributable to both improvement of diagnostic procedures and environmental factors. Among the modifiable risk factors, insulin resistance might influence the development of TC. A relationship between circadian clock machinery disfunction and TC has recently been proposed. The circadian clock machinery comprises a set of rhythmically expressed genes responsible for circadian rhythms. Perturbation of this system contributes to the development of pathological states such as cancer. Several clock genes have been found deregulated upon thyroid nodule malignant transformation. The molecular mechanisms linking circadian clock disruption and TC are still unknown but could include insulin resistance. Circadian misalignment occurring during shift work, jet lag, high fat food intake, is associated with increased insulin resistance. This metabolic alteration, in turn, is associated with a well-known risk factor for TC i.e., hyperthyrotropinemia, which could also be induced by sleep disturbances. In this review, we describe the mechanisms controlling the circadian clock function and its involvement in the cell cycle, stemness and cancer. Moreover, we discuss the evidence supporting the link between circadian clockwork disruption and TC development/progression, highlighting its potential implications for TC prevention, diagnosis and therapy.

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Non-Coding RNAs: Uncharted Mediators of Thyroid Cancer Pathogenesis

Cancers ◽

10.3390/cancers12113264 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3264

Author(s):

Hossein Tabatabaeian ◽

Samantha Peiling Yang ◽

Yvonne Tay

Keyword(s):

Thyroid Cancer ◽

Cancer Patients ◽

Molecular Mechanisms ◽

Endocrine System ◽

Circular Rnas ◽

Poor Overall Survival ◽

Cancer Pathogenesis ◽

Critical Issues ◽

Non Coding Rnas

Thyroid cancer is the most prevalent malignancy of the endocrine system and the ninth most common cancer globally. Despite the advances in the management of thyroid cancer, there are critical issues with the diagnosis and treatment of thyroid cancer that result in the poor overall survival of undifferentiated and metastatic thyroid cancer patients. Recent studies have revealed the role of different non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) that are dysregulated during thyroid cancer development or the acquisition of resistance to therapeutics, and may play key roles in treatment failure and poor prognosis of the thyroid cancer patients. Here, we systematically review the emerging roles and molecular mechanisms of ncRNAs that regulate thyroid tumorigenesis and drug response. We then propose the potential clinical implications of ncRNAs as novel diagnostic and prognostic biomarkers for thyroid cancer.

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Osteopontin Expression in Thyroid Cancer: Deciphering EMT-Related Molecular Mechanisms

Biomedicines ◽

10.3390/biomedicines9101372 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1372

Author(s):

Bruna Prunes Pena Baroni Viana ◽

Amanda Vitória Pampolha Gomes ◽

Etel Rodrigues Pereira Gimba ◽

Luciana Bueno Ferreira

Keyword(s):

Thyroid Cancer ◽

Cancer Progression ◽

Molecular Mechanisms ◽

Epithelial Mesenchymal Transition ◽

Endocrine System ◽

Good Prognosis ◽

Thyroid Tumor ◽

Diagnostic Tools ◽

Matricellular Protein ◽

Mesenchymal Transition

Thyroid cancer is the most common tumor arising from the endocrine system and generally presents good prognosis. However, its aggressive subtypes are related to therapeutic resistance and early metastasis. Epithelial–mesenchymal transition (EMT) and its reverse process, the mesenchymal–epithelial transition (MET), are key events mediating cancer progression, including in thyroid cancer. The matricellular protein osteopontin (OPN) has been reported as a master regulator of EMT in many tumor types. Although high OPN expression has been described and associated with important aspects of thyroid cancer progression, there is no clear evidence regarding OPN as a regulator of EMT in thyroid cancer. Thus, taking together the known roles of OPN in the modulation of EMT in cancer and the information reporting the expression of OPN in thyroid tumor progression, this review aims at summarizing and discussing data related to EMT in thyroid cancer and its putative relation to the roles of OPN in the development of thyroid cancer. These data provide new insights into the molecular mechanisms by which OPN could potentially modulate EMT in thyroid tumors, generating evidence for future studies that may contribute to new therapeutic, prognostic and/or diagnostic tools.

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Assessment Of Plasma B-Catenin Concentration As Biomarker Of Thyroid Cancer*

Polish Journal of Surgery ◽

10.1515/pjs-2015-0067 ◽

2015 ◽

Vol 87 (7) ◽

Cited By ~ 1

Author(s):

Michał Bełdowski

Keyword(s):

Thyroid Cancer ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Histopathological Examination ◽

Nodular Goiter ◽

Diagnostic Methods ◽

Control Group ◽

Papillary Thyroid ◽

It Use ◽

Cellular Expression

AbstractNew diagnostic methods for thyroid diseases are still being searched for. Immunohistochemical diagnosis is expanded by the introduction of new biomarkers including ß-catenin (B-Cat). Associations are indicated between the cellular expression of this biomarker and tumor stage, nodal metastases and the degree of tumor cell differentiation. Reports are scarce regarding the plasma level of this biomarker in malignant neoplastic diseases.was to analyze the plasma B-Cat concentration and the possibility of it use in the diagnostics of patients with nodular goiter and papillary thyroid carcinoma.Plasma B-Cat concentration was determined in 64 patients with goiter and 15 healthy volunteers. The final histopathological examination revealed 41 cases of papillary thyroid carcinoma (PTC) and 13 cases of nodular goiter (NG).A significant increase in B-Cat (p <0.05) in both groups compared to the control group. No differences in the concentrations of biomarker was demonstrated between the PTC and NG groups. After determining the AUC for the tested biomarker, the B-Cat ratio of the area value 0.721 was the strong diagnostic test.Changes in the plasma B-Cat concentration can be the biomarker of thyroid cancer but it cannot be used for the detection of papillary thyroid carcinoma becouse of concomitant tumor-like lesions in the thyroid gland.

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