Thyrotrophin receptors in normal and neoplastic (primary and metastatic) canine thyroid tissue

1992 ◽  
Vol 132 (3) ◽  
pp. 461-468 ◽  
Author(s):  
C. P. Verschueren ◽  
G. R. Rutteman ◽  
J. H. Vos ◽  
J. E. Van Dijk ◽  
T. W. A. de Bruin
Keyword(s):  
Thyroid Carcinoma ◽  
Binding Affinity ◽  
Receptor Binding ◽  
Binding Sites ◽  
Thyroid Tissue ◽  
Thyroid Neoplasms ◽  
Tsh Receptor ◽  
Normal Thyroid ◽  
Thyroid Carcinomas ◽  
Receptor Number

ABSTRACT Thyrotrophin (TSH) is the conditional growth factor of thyroid epithelial cells. Abnormalities in TSH-receptor binding such as a low receptor number or low binding affinity may be a marker of thyroid carcinoma or metastases, or may exhibit a relationship with the functional variability of such tissues. The dog was used as a model to characterize TSH-receptor binding in normal thyroid tissues, naturally occurring thyroid neoplasms and distant metastases. In normal dog thyroid tissues, specific 125I-labelled TSH binding ranged from 2·7 to 15·5%, and low cross-reactivity with bovine LH (0·023%) was observed. One class of TSH-binding sites was found in eight normal thyroid tissues and 22 thyroid carcinomas; two normal thyroid tissues and one tumour exhibited two classes of binding sites. The concentration of binding sites was lower in the five carcinomas with reduced pertechnetate uptake (0·09 pmol/mg protein) than in the five thyroid neoplasms with increased uptake (0·19 pmol/mg) (P= 0·055). Compared with the original carcinoma tissues, TSH binding revealed a reduced binding affinity in eight out of eleven metastases. Two metastases showed a complete absence of TSH binding, suggesting that they were not dependent on TSH for growth. We conclude that one class of TSH-binding site is predominant in normal dog thyroid tissues and dog thyroid carcinomas. TSH could therefore contribute, at least in theory, to further growth of primary dog thyroid carcinomas. Secondly, assays measuring TSH binding may not be able to discriminate between malignant and benign dog thyroid tumours. TSH receptor number or affinity may be related to the functional variability of thyroid neoplasms. The absence of TSH binding in some metastases demonstrated that this characteristic can be acquired during the natural history of a differentiated thyroid carcinoma. Journal of Endocrinology (1992) 132, 461–468

scholarly journals Deregulation of microRNA expression in follicular cell-derived human thyroid carcinomas

2010 ◽  
Vol 17 (1) ◽  
pp. F91-F104 ◽  
Author(s):  
Pierlorenzo Pallante ◽  
Rosa Visone ◽  
Carlo Maria Croce ◽  
Alfredo Fusco
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Thyroid Tissue ◽  
Endocrine System ◽  
Follicular Carcinoma ◽  
Thyroid Neoplasms ◽  
Anaplastic Thyroid Cancer ◽  
Microrna Expression ◽  
Human Thyroid ◽  
Thyroid Carcinomas

Carcinoma of the thyroid gland is an uncommon cancer, but one of the most frequent malignancies of the endocrine system. Most thyroid cancers are derived from the follicular cells. Follicular carcinoma is considered more malignant than papillary thyroid carcinoma (PTC), and anaplastic thyroid cancer (ATC) is one of the most lethal human cancers. Even though several genetic lesions have been already described in human thyroid cancer, particularly in the papillary histotype, the mechanisms underlying the development of these neoplasias are still far from being completely elucidated. Some years ago, several studies were undertaken to analyze the expression of microRNAs (miRNAs or miRs) in thyroid carcinoma to evaluate a possible role of their deregulation in the process of carcinogenesis. These studies showed an aberrant microRNA expression profile that distinguishes unequivocally among PTC, ATC, and normal thyroid tissue. Here, other than summarizing the current findings on microRNA expression in human thyroid carcinomas, we discuss the mechanisms by which microRNA deregulation may play a role in thyroid carcinogenesis, and the possible use of microRNA knowledge in the diagnosis and therapy of thyroid neoplasms.

scholarly journals Identification of a paired box gene 8–peroxisome proliferator-activated receptor gamma (PAX8–PPARγ) rearrangement mosaicism in a patient with an autonomous functioning follicular thyroid carcinoma bearing an activating mutation in the TSH receptor

2010 ◽  
Vol 17 (3) ◽  
pp. 599-610 ◽  
Author(s):  
J Lado-Abeal ◽  
R Celestino ◽  
S B Bravo ◽  
M E R Garcia-Rendueles ◽  
J de la Calzada ◽  
...  
Keyword(s):  
Growth Factors ◽  
Thyroid Carcinoma ◽  
Uterine Leiomyoma ◽  
Follicular Thyroid Carcinoma ◽  
Thyroid Tissue ◽  
Tsh Receptor ◽  
Peroxisome Proliferator ◽  
Normal Thyroid Tissue ◽  
Peroxisome Proliferator Activated Receptor ◽  
Normal Thyroid

Our main objective was to search for mutations in candidate genes and for paired box gene 8–peroxisome proliferator-activated receptor gamma (PAX8–PPARγ) rearrangement in a well-differentiated angioinvasive follicular thyroid carcinoma (FTC) causing hyperthyroidism. DNA and RNA were extracted from the patient's thyroid tumor, as well as ‘normal’ thyroid tissue, and from peripheral blood lymphocytes (PBLs) of the patient, her daughter, and two siblings. Nuclear isolation was extracted from the patient's tumor, ’normal’ thyroid tissue, PBLs, and uterine leiomyoma tissue. TSH receptor (TSHR), RAS, and BRAF genes were sequenced. We searched for PAX8–PPARγ in thyroid, PBL, and uterine leiomyoma samples from the patient and family members. Proliferative effects of detected mutants on non-transformed human thyrocytes cultures. An activating TSHR mutation, M453T, was detected in the tumor. PAX8 (exons 1–8+10)–PPARγ was found in all tested patient's tissues. A second rearrangement, PAX8 (exons 1–8)–PPARγ, was detected in the patient's normal thyroid tissue. Under deprived medium condition, co-transfection of PAX8–PPARγ and TSHR–M453T dramatically increased the number of thyrocytes, an effect that it was not observed with TSHR wild-type (WT); under complete medium conditions, co-transfection of PAX8–PPARγ with either TSHR–M453T or TSHR–WT inhibited cell proliferation. We report a patient with hyperthyroidism due to a FTC bearing an activating TSHR mutation and PAX8–PPARγ rearrangements. PAX8–PPARγ was present as a mosaicism affecting tissues from endodermal and mesodermal origin. PAX8–PPARγ and TSHR–M453T inhibited or promoted thyrocyte proliferation depending on medium conditions. The activating TSHR mutation could promote in vivo FTC development in PAX8–PPARγ-positive thyrocytes under poor blood supply with deprivation of growth factors but restraint the tumor growth when growth factors are supplied.

The CCK2-receptor is expressed in human medullary thyroid carcinomas as well as in normal thyroid tissue

2001 ◽  
Vol 120 (5) ◽  
pp. A507-A507
Author(s):  
M BLAEKER ◽  
A WEERTH ◽  
L JONAS ◽  
M TOMETTEN ◽  
M SCHUTZ ◽  
...  
Keyword(s):  
Thyroid Tissue ◽  
Normal Thyroid Tissue ◽  
Normal Thyroid ◽  
Medullary Thyroid ◽  
Thyroid Carcinomas ◽  
Cck2 Receptor ◽  
Medullary Thyroid Carcinomas

scholarly journals A Pro-Tumorigenic Effect of Heparanase 2 (Hpa2) in Thyroid Carcinoma Involves Its Localization to the Nuclear Membrane

2021 ◽  
Vol 11 ◽  
Author(s):  
Itai Margulis ◽  
Inna Naroditsky ◽  
Miriam Gross-Cohen ◽  
Neta Ilan ◽  
Israel Vlodavsky ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Lymph Nodes ◽  
Nuclear Membrane ◽  
Tumor Metastasis ◽  
Cellular Localization ◽  
Thyroid Tissue ◽  
Clinicopathological Parameters ◽  
Regional Lymph Nodes ◽  
Normal Thyroid

Activity of the endo-beta-glucuronidase heparanase, capable of cleaving heparan sulfate (HS), is most often elevated in many types of tumors, associating with increased tumor metastasis and decreased patients’ survival. Heparanase is therefore considered to be a valid drug target, and heparanase inhibitors are being evaluated clinically in cancer patients. Heparanase 2 (Hpa2) is a close homolog of heparanase that gained very little attention, likely because it lacks HS-degrading activity typical of heparanase. The role of Hpa2 in cancer was not examined in detail. In head and neck cancer, high levels of Hpa2 are associated with decreased tumor cell dissemination to regional lymph nodes and prolonged patients’ survival, suggesting that Hpa2 functions to attenuate tumor growth. Here, we examined the role of Hpa2 in normal thyroid tissue and in benign thyroid tumor, non-metastatic, and metastatic papillary thyroid carcinoma (PTC) utilizing immunostaining in correlation with clinicopathological parameters. Interestingly, we found that Hpa2 staining intensity does not significantly change in the transition from normal thyroid gland to benign, non-metastatic, or metastatic thyroid carcinoma. Remarkably, we observed that in some biopsies, Hpa2 is accumulating on the membrane (envelop) of the nucleus and termed this cellular localization NM (nuclear membrane). Notably, NM localization of Hpa2 occurred primarily in metastatic PTC and was associated with an increased number of positive (metastatic) lymph nodes collected at surgery. These results describe for the first time unrecognized localization of Hpa2 to the nuclear membrane, implying that in PTC, Hpa2 functions to promote tumor metastasis.

scholarly journals Na+/I− Symporter Distribution in Human Thyroid Tissues: An Immunohistochemical Study1

1998 ◽  
Vol 83 (11) ◽  
pp. 4102-4106 ◽  
Author(s):  
Bernard Caillou ◽  
Frédéric Troalen ◽  
Eric Baudin ◽  
Monique Talbot ◽  
Sébastiano Filetti ◽  
...  
Keyword(s):  
Normal Tissue ◽  
Close Contact ◽  
Basolateral Membrane ◽  
Thyroid Tissue ◽  
Follicular Carcinoma ◽  
Thyroid Neoplasms ◽  
Human Thyroid ◽  
Follicular Cells ◽  
Normal Thyroid ◽  
Well Differentiated

Antipeptide antibodies raised against the carboxyl-terminal region of the human sodium/iodide (Na+/I−) symporter (hNIS) were used to investigate by immunohistochemistry the presence and distribution of the hNIS protein in normal thyroid tissues, in some pathological nonneoplastic thyroid tissues, and in different histotypes of thyroid neoplasms. In normal thyroid tissue, staining of hNIS protein was heterogeneous and limited to a minority of follicular cells that were in close contact with capillary vessels. In positive cells, immunostaining was limited to the basolateral membrane. In contrast, in Graves’ disease the majority of follicular cells expressed the hNIS protein. In autoimmune thyroiditis, the number of hNIS-positive cells, was similar to that found in normal tissue. These positive cells were found essentially close to lymphocytic infiltrates. This observation supports the concept of hNIS as an autoantigen. In diffuse nodular hyperplasia, hNIS staining was heterogeneous, but the number of hNIS-positive cells exceeded that found in normal tissue. In well differentiated follicular or papillary carcinoma, the number of hNIS-positive cells was significantly lower than in normal tissue. In poorly differentiated follicular carcinoma, the number of hNIS-positive cells was less than that found in well differentiated carcinoma, or there were no positive cells. Interestingly, in all of these thyroid tissues, the number of follicular cells exhibiting TSH receptor (TSHR) immunoreactivity was greater than the number of hNIS-positive cells. As hNIS expression appears to be related to TSHR stimulation, the decreased number of TSHR-positive cells in cancers may contribute to the reduced capacity of neoplastic cells to concentrate iodide. In one patient with a follicular cancer with an absence of hNIS immunostaining, the total body 131I scan showed no uptake in metastatic tissue. In three cancers with positive hNIS cells, the 131I scan showed uptake in lymph node metastases. This suggests that immunodetection of hNIS could predict radioiodine uptake in thyroid cancers.

scholarly journals BRAF Mutations in Papillary Thyroid Carcinomas Inhibit Genes Involved in Iodine Metabolism

2007 ◽  
Vol 92 (7) ◽  
pp. 2840-2843 ◽  
Author(s):  
C. Durante ◽  
E. Puxeddu ◽  
E. Ferretti ◽  
R. Morisi ◽  
S. Moretti ◽  
...  
Keyword(s):  
Glucose Transporter ◽  
Thyroid Tissue ◽  
Braf V600e ◽  
Mrna Levels ◽  
Papillary Thyroid ◽  
Sodium Iodide Symporter ◽  
Braf Mutations ◽  
Normal Thyroid ◽  
Thyroid Carcinomas ◽  
Iodine Metabolism

Abstract Context: BRAF mutations are common in papillary thyroid carcinomas (PTCs). By affecting the expression of genes critically related to the development and differentiation of thyroid cancer, they may influence the prognosis of these tumors. Objective: Our objective was to characterize the expression of thyroid-specific genes associated with BRAF mutation in PTCs. Design/Setting and Patients: We examined the expression of key markers of thyrocyte differentiation in 56 PTCs with BRAF mutations (BRAF-mut) and 37 with wild-type BRAF (BRAF-wt). Eight samples of normal thyroid tissue were analyzed as controls. Quantitative PCR was used to measure mRNA levels for the sodium/iodide symporter (NIS), apical iodide transporter (AIT-B), thyroglobulin (Tg), thyroperoxidase (TPO), TSH receptor (TSH-R), the transcription factor PAX8, and glucose transporter type 1 (Glut1). NIS protein expression and localization was also analyzed by immunohistochemistry. Results: mRNA levels for all thyroid-specific genes were reduced in all PTCs vs. normal thyroid tissues. NIS, AIT-B, Tg, and TPO expression was significantly lower in BRAF-mut tumors than in the BRAF-wt group. Glut-1 transcript levels were increased in all PTCs, and additional increases were noted in BRAF-mut tumors. In both tumor subsets, the NIS protein that was expressed was abnormally retained in the cytoplasm. Conclusion: BRAF V600E mutation in PTCs is associated with reduced expression of key genes involved in iodine metabolism. This effect may alter the effectiveness of diagnostic and/or therapeutic use of radioiodine in BRAF-mut PTCs.

scholarly journals Vascular endothelial growth factor gene and protein: strong expression in thyroiditis and thyroid carcinoma

1999 ◽  
Vol 161 (1) ◽  
pp. 41-49 ◽  
Author(s):  
M Klein ◽  
E Picard ◽  
JM Vignaud ◽  
B Marie ◽  
L Bresler ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Thyroid Carcinoma ◽  
Vascular Endothelial ◽  
Vegf Mrna ◽  
Normal Thyroid ◽  
Thyroid Carcinomas ◽  
Endothelial Growth Factor ◽  
Immunostaining Score

Angiogenesis is implicated in several pathological conditions, such as inflammation and tumor growth. Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is a potent stimulator of endothelial cell proliferation in vitro and in vivo. The present work aimed to compare VEGF expression in human normal thyroid glands, thyroiditis tissue and thyroid carcinomas using immunohistochemistry and in situ hybridization (ISH). Both chronic lymphocytic thyroiditis and differentiated thyroid carcinomas were found to strongly express VEGF mRNA and encode larger amounts of VEGF than normal thyroid tissue as attested by a VEGF immunostaining score. In addition, tumor samples from patients with metastases showed a higher immunostaining score than their non-metastatic counterparts (P<0.05). Carcinomas with the greatest contents of VEGF mRNA and VEGF protein had the most intense mitogenic activity. Special focus on endothelial cells showed intense mitogenic activity in neoplastic tissues in contrast to the total quiescence of endothelial cells in non-tumoral tissues. An intense VEGF production by differentiated thyroid carcinoma, attested either by a higher immunostaining score or a strong VEGF mRNA expression using ISH, could be a promising marker of tumor aggressiveness and may also be useful as a predictor of metastatic potential.

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 Quantitative and qualitative differences in protein expression between papillary thyroid carcinoma and normal thyroid tissue

2006 ◽  
Vol 45 (8) ◽  
pp. 613-626 ◽  
Author(s):  
Lewis M. Brown ◽  
Steve M. Helmke ◽  
Stephen W. Hunsucker ◽  
Romana T. Netea-Maier ◽  
Simon A. Chiang ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Protein Expression ◽  
Thyroid Tissue ◽  
Papillary Thyroid ◽  
Normal Thyroid Tissue ◽  
Normal Thyroid

scholarly journals Differential expression of IgG Fc binding protein (FcgammaBP) in human normal thyroid tissue, thyroid adenomas and thyroid carcinomas

2002 ◽  
Vol 174 (3) ◽  
pp. 517-524 ◽  
Author(s):  
N O'Donovan ◽  
A Fischer ◽  
EM Abdo ◽  
F Simon ◽  
HJ Peter ◽  
...  
Keyword(s):  
Differential Expression ◽  
Binding Protein ◽  
Thyroid Tissue ◽  
Differentially Expressed ◽  
Normal Thyroid Tissue ◽  
Altered Expression ◽  
Normal Thyroid ◽  
Thyroid Carcinomas ◽  
New Genes ◽  
Thyroid Adenomas

The genetic events involved in thyroid carcinogenesis are still incompletely understood. Several rearrangements and mutations of oncogenes have been implicated in the development of thyroid papillary carcinomas, follicular adenomas and carcinomas. However, none of these molecular alterations is suitable either as a general marker for the diagnosis of thyroid carcinomas or to differentiate between thyroid follicular adenomas and carcinomas. In order to identify new genes with altered expression which could serve as such markers, we analyzed RNA from thyroid tumor and normal tissue using a novel technique called restriction-mediated differential display. Several differentially expressed genes were identified, including the gene for IgG Fc binding protein (FcgammaBP). Differential expression of FcgammaBP was confirmed by quantitative real-time RT-PCR. Our experiments showed that IgG Fc binding protein (FcgammaBP) is differentially expressed in normal thyroid tissue, thyroid adenomas and thyroid carcinomas. While the FcgammaBP gene is constitutively expressed in normal thyroid tissue, its expression is significantly increased in follicular thyroid adenomas and significantly decreased in papillary and follicular thyroid carcinomas. Thus, measurement of the expression levels of FcgammaBP in thyroid biopsies might help to make the otherwise difficult distinction between a thyroid follicular adenoma and a follicular carcinoma.

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