Genetic Alterations Involved in the Transition from Well-Differentiated to Poorly Differentiated and Anaplastic Thyroid Carcinomas

2004 ◽  
Vol 15 (4) ◽  
pp. 319-328 ◽  
Author(s):  
Yuri E. Nikiforov
Keyword(s):  
Genetic Alterations ◽  
Thyroid Carcinomas ◽  
Poorly Differentiated ◽  
Well Differentiated

scholarly journals MicroRNA profile of poorly differentiated thyroid carcinomas: new diagnostic and prognostic insights

2014 ◽  
Vol 52 (2) ◽  
pp. 181-189 ◽  
Author(s):  
Matthias S Dettmer ◽  
Aurel Perren ◽  
Holger Moch ◽  
Paul Komminoth ◽  
Yuri E Nikiforov ◽  
...  
Keyword(s):  
Mirna Expression ◽  
Thyroid Tissue ◽  
Mirna Expression Profile ◽  
Normal Thyroid ◽  
Thyroid Carcinomas ◽  
Microrna Profile ◽  
Poorly Differentiated ◽  
The Difference ◽  
Well Differentiated ◽  
Differentiated Thyroid Cancers

The diagnosis of conventional and oncocytic poorly differentiated (oPD) thyroid carcinomas is difficult. The aim of this study is to characterise their largely unknown miRNA expression profile and to compare it with well-differentiated thyroid tumours, as well as to identify miRNAs which could potentially serve as diagnostic and prognostic markers. A total of 14 poorly differentiated (PD), 13 oPD, 72 well-differentiated thyroid carcinomas and eight normal thyroid specimens were studied for the expression of 768 miRNAs using PCR-Microarrays. MiRNA expression was different between PD and oPD thyroid carcinomas, demonstrating individual clusters on the clustering analysis. Both tumour types showed upregulation of miR-125a-5p, -15a-3p, -182, -183-3p, -222, -222-5p, and downregulation of miR-130b, -139-5p, -150, -193a-5p, -219-5p, -23b, -451, -455-3p and of miR-886-3p as compared with normal thyroid tissue. In addition, the oPD thyroid carcinomas demonstrated upregulation of miR-221 and miR-885-5p. The difference in expression was also observed between miRNA expression in PD and well-differentiated tumours. The CHAID algorithm allowed the separation of PD from well-differentiated thyroid carcinomas with 73–79% accuracy using miR-23b and miR-150 as a separator. Kaplan–Meier and multivariate analysis showed a significant association with tumour relapses (for miR-23b) and with tumour-specific death (for miR-150) in PD and oPD thyroid carcinomas. MiRNA expression is different in conventional and oPD thyroid carcinomas in comparison with well-differentiated thyroid cancers and can be used for discrimination between these tumour types. The newly identified deregulated miRNAs (miR-150, miR-23b) bear the potential to be used in a clinical setting, delivering prognostic and diagnostic informations.

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.

scholarly journals Genetic Alterations in Poorly Differentiated and Undifferentiated Thyroid Carcinomas

2011 ◽  
Vol 12 (8) ◽  
pp. 609-617 ◽  
Author(s):  
Paula Soares ◽  
Jorge Lima ◽  
Ana Preto ◽  
Patricia Castro ◽  
Joao Vinagre ◽  
...  
Keyword(s):  
Genetic Alterations ◽  
Thyroid Carcinomas ◽  
Poorly Differentiated

scholarly journals PFKFB2 Promoter Hypomethylation as Recurrence Predictive Marker in Well-Differentiated Thyroid Carcinomas

2019 ◽  
Vol 20 (6) ◽  
pp. 1334 ◽  
Author(s):  
Mateus Camargo Barros-Filho ◽  
Larissa Barreto Menezes de Lima ◽  
Mariana Bisarro dos Reis ◽  
Julia Bette Homem de Mello ◽  
Caroline Moraes Beltrami ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Predictive Marker ◽  
Recurrence Risk ◽  
Good Prognosis ◽  
Braf V600e ◽  
Free Survival ◽  
Thyroid Carcinomas ◽  
Potential Applicability ◽  
Poorly Differentiated ◽  
Well Differentiated

Despite the low mortality rates, well-differentiated thyroid carcinomas (WDTC) frequently relapse. BRAF and TERT mutations have been extensively related to prognosis in thyroid cancer. In this study, the methylation levels of selected CpGs (5-cytosine-phosphate-guanine-3) comprising a classifier, previously reported by our group, were assessed in combination with BRAF and TERT mutations. We evaluated 121 WDTC, three poorly-differentiated/anaplastic thyroid carcinomas (PDTC/ATC), 22 benign thyroid lesions (BTL), and 13 non-neoplastic thyroid (NT) tissues. BRAF (V600E) and TERT promoter (C228T and C250T) mutations were tested by pyrosequencing and Sanger sequencing, respectively. Three CpGs mapped in PFKFB2, ATP6V0C, and CXXC5 were evaluated by bisulfite pyrosequencing. ATP6V0C hypermethylation and PFKFB2 hypomethylation were detected in poor-prognosis (PDTC/ATC and relapsed WDTC) compared with good-prognosis (no relapsed WDTC) and non-malignant cases (NT/BTL). CXXC5 was hypomethylated in both poor and good-prognosis cases. Shorter disease-free survival was observed in WDTC patients presenting lower PFKFB2 methylation levels (p = 0.004). No association was observed on comparing BRAF (60.7%) and TERT (3.4%) mutations and prognosis. Lower PFKFB2 methylation levels was an independent factor of high relapse risk (Hazard Ratio = 3.2; CI95% = 1.1–9.5). PFKFB2 promoter methylation analysis has potential applicability to better stratify WDTC patients according to the recurrence risk, independently of BRAF and TERT mutations.

scholarly journals Characterization of thyroid cancer driven by known and novel ALK fusions

2019 ◽  
Vol 26 (11) ◽  
pp. 803-814 ◽  
Author(s):  
Federica Panebianco ◽  
Alyaksandr V Nikitski ◽  
Marina N Nikiforova ◽  
Cihan Kaya ◽  
Linwah Yip ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Nodules ◽  
Thyroid Neoplasms ◽  
Thyroid Carcinomas ◽  
Fine Needle Aspirates ◽  
Target Spectrum ◽  
Radiation History ◽  
Rare Gene ◽  
Poorly Differentiated ◽  
Well Differentiated

ALK fusions are found in various tumors, including thyroid cancer, and serve as a diagnostic marker and therapeutic target. Spectrum and outcomes of ALK fusions found in thyroid nodules and cancer are not fully characterized. We report a series of 44 ALK-translocated thyroid neoplasms, including 31 identified preoperatively in thyroid fine-needle aspirates (FNA). The average patients’ age was 43 years (range, 8–76 years); only one with radiation history. All 19 resected thyroid nodules with ALK fusion identified preoperatively were malignant. Among nodules with known surgical pathology (n = 32), 84% were papillary thyroid carcinomas (PTCs) and 16% poorly differentiated thyroid carcinomas (PDTCs). PTCs showed infiltrative growth with follicular architecture seen exclusively (30%) or in combination with papillary and/or solid growth (37%). Tumor multifocality was seen in 10 (31%) PTC cases. Most PDTC had a well-differentiated PTC component. Lymph node metastases were identified in 10/18 (56%) patients with neck dissection. The most common ALK fusion partners were STRN (n = 22) and EML4 (n = 17). In five cases, novel ALK fusion partners were discovered. All five PDTCs carried STRN-ALK fusion. On follow-up, ten patients were free of disease at 2–108 months, whereas two patients with PDTC died of disease. In summary, ALK fusion-positive thyroid carcinomas are typically infiltrative PTC with common follicular growth, which may show tumor dedifferentiation associated with increased mortality. Compared to EML4-ALK, STRN-ALK may be more common in PDTC, and ~10% of ALK fusions occur to rare gene partners. When ALK fusion is detected preoperatively in FNA samples, malignancy should be expected.

How molecular pathology is changing and will change the therapeutics of patients with follicular cell-derived thyroid cancer: Table 1

2009 ◽  
Vol 62 (5) ◽  
pp. 414-421 ◽  
Author(s):  
J Pinto Couto ◽  
H Prazeres ◽  
P Castro ◽  
J Lima ◽  
V Máximo ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Molecular Pathology ◽  
Genetic Alterations ◽  
Follicular Cell ◽  
Braf Mutations ◽  
Thyroid Carcinomas ◽  
Ras Mutations ◽  
Molecular Alterations ◽  
Dna Deletions ◽  
Well Differentiated

Well-differentiated thyroid carcinomas comprise two well-defined histological types: papillary and follicular (PTCs and FTCs, respectively). Despite being derived from the same cell (thyroid follicular cell), these two types of tumour accumulate distinct genetic abnormalities during progression. The molecular pathology of thyroid cancer is now better understood because of our ability to identify RET/PTC rearrangements and BRAF mutations in the aetiopathogenesis of the large majority of PTCs and the high prevalence of RAS mutations and PAX8/PPARγ rearrangements in follicular patterned carcinomas (FTCs and follicular variant of PTCs). This review summarises most of the molecular alterations currently used as targets for new biological treatments and looks at some of the changes that are already occurring or may occur in the treatment of patients with thyroid cancer. For simplicity, the review is divided up according to the major genetic alterations identified in well-differentiated thyroid carcinomas (RET/PTC rearrangements, BRAF mutations, RAS mutations and mitochondrial DNA deletions and mutations) and their respective treatments.

scholarly journals Comprehensive Literature Review: Recent Advances in Diagnosing and Managing Patients with Poorly Differentiated Thyroid Carcinoma

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Jack Hannallah ◽  
Jessica Rose ◽  
Marlon A. Guerrero
Keyword(s):  
Treatment Approach ◽  
Survival Rates ◽  
Multimodality Treatment ◽  
Differentiated Thyroid Carcinoma ◽  
Poor Survival ◽  
Thyroid Carcinomas ◽  
Comprehensive Literature Review ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Therapeutic Tools

Poorly differentiated thyroid carcinomas are a rare form of thyroid carcinomas; they display an intermediate behavior between well-differentiated and anaplastic thyroid carcinomas. PDTCs are more aggressive than the well-differentiated, but less aggressive than the undifferentiated or anaplastic, forms. No clinical features can accurately diagnose poorly differentiated thyroid carcinomas. Thus, the results of histocytology, immunohistochemistry, and molecular genetics tests aid in diagnosis. Given the aggressiveness of poorly differentiated thyroid carcinomas and the poor survival rates in patients who undergo surgery alone, a multimodality treatment approach is required. We conducted a comprehensive review of the current diagnostic and therapeutic tools in the management of patients with poorly differentiated thyroid carcinomas.

scholarly journals Molecular Pathology of Poorly Differentiated and Anaplastic Thyroid Cancer: What Do Pathologists Need to Know?

2021 ◽  
Vol 32 (1) ◽  
pp. 63-76 ◽  
Author(s):  
Marco Volante ◽  
Alfred K. Lam ◽  
Mauro Papotti ◽  
Giovanni Tallini
Keyword(s):  
Molecular Pathology ◽  
Wide Spectrum ◽  
Biological Effects ◽  
Genetic Alterations ◽  
Epigenetic Modifications ◽  
Mismatch Repair Gene ◽  
Repair Gene ◽  
Thyroid Carcinomas ◽  
Poorly Differentiated ◽  
The Impact

AbstractThe molecular characterization of poorly and anaplastic thyroid carcinomas has been greatly improved in the last years following the advent of high throughput technologies. However, with special reference to genomic data, the prevalence of reported alterations is partly affected by classification criteria. The impact of molecular pathology in these tumors is multifaceted and bears diagnostic, prognostic, and predictive implications although its use in the clinical practice is not completely assessed. Genomic profiling data claim that genetic alterations in poorly differentiated and anaplastic thyroid carcinomas include “Early” and “Late” molecular events, which are consistent with a multi-step model of progression. “Early” driver events are mostly RAS and BRAF mutations, whereas “Late” changes include above all TP53 and TERT promoter mutations, as well as dysregulation of gene involved in the cell cycle, chromatin remodeling, histone modifications, and DNA mismatch repair. Gene fusions are rare but represent relevant therapeutic targets. Epigenetic modifications are also playing a relevant role in poorly differentiated and anaplastic thyroid carcinomas, with altered regulation of either genes by methylation/deacetylation or non-coding RNAs. The biological effects of epigenetic modifications are not fully elucidated but interfere with a wide spectrum of cellular functions. From a clinical standpoint, the combination of genomic and epigenetic data shows that several molecular alterations affect druggable cellular pathways in poorly differentiated and anaplastic thyroid carcinomas, although the clinical impact of molecular typing of these tumors in terms of predictive biomarker testing is still under exploration.

Motility of leukemic lymphocytes

1990 ◽  
Vol 48 (3) ◽  
pp. 368-369
Author(s):  
Manoj Raje ◽  
Karvita B. Ahluwalia
Keyword(s):  
Quantitative Data ◽  
Laser Doppler Velocimetry ◽  
Acute Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Cellular Space ◽  
Differentiated Cells ◽  
Poorly Differentiated ◽  
Solid Tissues ◽  
Well Differentiated ◽  
Reduced Mobility

In Acute Lymphocytic Leukemia motility of lymphocytes is associated with dissemination of malignancy and establishment of metastatic foci. Normal and leukemic lymphocytes in circulation reach solid tissues where due to in adequate perfusion some cells get trapped among tissue spaces. Although normal lymphocytes reenter into circulation leukemic lymphocytes are thought to remain entrapped owing to reduced mobility and form secondary metastasis. Cell surface, transmembrane interactions, cytoskeleton and level of cell differentiation are implicated in lymphocyte mobility. An attempt has been made to correlate ultrastructural information with quantitative data obtained by Laser Doppler Velocimetry (LDV). TEM of normal & leukemic lymphocytes revealed heterogeneity in cell populations ranging from well differentiated (Fig. 1) to poorly differentiated cells (Fig. 2). Unlike other cells, surface extensions in differentiated lymphocytes appear to originate by extrusion of large vesicles in to extra cellular space (Fig. 3). This results in persistent unevenness on lymphocyte surface which occurs due to a phenomenon different from that producing surface extensions in other cells.

Molecular genetic markers for thyroid FNAB

2015 ◽  
Vol 54 (03) ◽  
pp. 94-100 ◽  
Author(s):  
P. B. Musholt ◽  
T. J. Musholt
Keyword(s):  
Genetic Markers ◽  
Thyroid Nodules ◽  
Molecular Genetic ◽  
Genetic Alterations ◽  
Diagnostic Tools ◽  
Ultrasound Screening ◽  
Thyroid Malignancy ◽  
Thyroid Carcinomas ◽  
Molecular Genetic Markers ◽  
The Impact

SummaryAim: Thyroid nodules > 1 cm are observed in about 12% of unselected adult employees aged 18–65 years screened by ultrasound scan (40). While intensive ultrasound screening leads to early detection of thyroid diseases, the determination of benign or malignant behaviour remains uncertain and may trigger anxieties in many patients and their physicians. A considerable number of thyroid resections are consecutively performed due to suspicion of malignancy in the detected nodes. Fine needle aspiration biopsy (FNAB) has been recommended for the assessment of thyroid nodules to facilitate detection of thyroid carcinomas but also to rule out malignancy and thereby avoid unnecessary thyroid resections. However, cytology results are dependent on experience of the respective cytologist and unfortunately inconclusive in many cases. Methods: Molecular genetic markers are already used nowadays to enhance sensitivity and specificity of FNAB cytology in some centers in Germany. The most clinically relevant molecular genetic markers as pre-operative diagnostic tools and the clinical implications for the intraoperative and postoperative management were reviewed. Results: Molecular genetic markers predominantly focus on the preoperative detection of thyroid malignancies rather than the exclusion of thyroid carcinomas. While some centers routinely assess FNABs, other centers concentrate on FNABs with cytology results of follicular neoplasia or suspicion of thyroid carcinoma. Predominantly mutations of BRAF, RET/PTC, RAS, and PAX8/PPARγ or expression of miRNAs are analyzed. However, only the detection of BRAF mutations predicts the presence of (papillary) thyroid malignancy with almost 98% probability, indicating necessity of oncologic thyroid resections irrespective of the cytology result. Other genetic alterations are associated with thyroid malignancy with varying frequency and achieve less impact on the clinical management. Conclusion: Molecular genetic analysis of FNABs is increasingly performed in Germany. Standardization, quality controls, and validation of various methods need to be implemented in the near future to be able to compare the results. With increasing knowledge about the impact of genetic alterations on the prognosis of thyroid carcinomas, recommendations have to be defined that may lead to individually optimized treatment strategies.

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