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 ◽  
...  

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.

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

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


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 ◽  
...  

Oncotarget ◽  
2016 ◽  
Vol 7 (20) ◽  
pp. 29677-29688 ◽  
Author(s):  
Roberto Ria ◽  
Vittorio Simeon ◽  
Assunta Melaccio ◽  
Giovanna Di Meo ◽  
Stefania Trino ◽  
...  

Author(s):  
Quan Wang ◽  
Yilin Shen ◽  
Bin Ye ◽  
Haixia Hu ◽  
Cui Fan ◽  
...  

2021 ◽  
Author(s):  
Yaoting Sun ◽  
Lu Li ◽  
Weigang Ge ◽  
Zhen Dong ◽  
Wei Liu ◽  
...  

Thyroid nodules occur in about 60% of the population. Current diagnostic strategies, however, often fail at distinguishing malignant nodules before surgery, thus leading to unnecessary, invasive treatments. As proteins are involved in all physio/pathological processes, a proteome investigation of biopsied nodules may help correctly classify and identify malignant nodules and discover therapeutic targets. Quantitative mass spectrometry data-independent acquisition (DIA) enables highly reproducible and rapid throughput investigation of proteomes. An exhaustive spectral library of thyroid nodules is essential for DIA yet still unavailable. This study presents a comprehensive thyroid spectral library covering five types of thyroid tissue: multinodular goiter, follicular adenoma, follicular and papillary thyroid carcinoma, and normal thyroid tissue. Our library includes 925,330 transition groups, 157,548 peptide precursors, 121,960 peptides, 9941 protein groups, and 9826 proteins from proteotypic peptides. This library resource was evaluated using three papillary thyroid carcinoma samples and their corresponding adjacent normal thyroid tissue, leading to effective quantification of up to 7863 proteins from biopsy-level thyroid tissues.


2001 ◽  
Vol 120 (5) ◽  
pp. A507-A507
Author(s):  
M BLAEKER ◽  
A WEERTH ◽  
L JONAS ◽  
M TOMETTEN ◽  
M SCHUTZ ◽  
...  

2021 ◽  
Author(s):  
Steven Raeymaeckers ◽  
Yannick De Brucker ◽  
Tim Vanderhasselt ◽  
Nico Buls ◽  
Johan De Mey

Abstract Background. 4DCT is a commonly performed examination in the management of primary hyperparathyroidism, combining three-dimensional imaging with enhancement over time as the fourth dimension. We propose a novel technique consisting of 16 different contrast phases, instead of three or four different phases. The main aim of this study was to see if this protocol allows for the detection of parathyroid adenomas within dose limits. Our secondary aim was examining the enhancement of parathyroid lesions over time.Methods. For this prospective study, we included 15 patients with primary hyperparathyroidism prior to surgery. We obtain a 4DCT with 16 different phases: an unenhanced phase followed by 11 consecutive arterial phases and 4 venous phases. Centered on the thyroid, continuous axial scanning is performed over a fixed 8cm or 16cm coverage volume after start of contrast administration.Results. In all patients an enlarged parathyroid can be demonstrated, mean lesion size is 13.6mm. Mean peak arterial peak enhancement for parathyroid lesions is 384 HU compared to 333 HU for the normal thyroid. No statistical difference could be found. Time to peak (TTP) is significantly earlier for parathyroid adenomas compared to normal thyroid tissue: 30.8s versus 32.3s (p value 0.008). Mean Slope of Increase (MSI) of the enhancement curve is significantly steeper compared to normal thyroid tissue: 29.8% versus 22.2% (p value 0.012). Mean dose length product was 890.7 mGy.cm with a calculated effective dose of 6.7 mSv.Conclusion. We propose a feasible 4DCT scanning-protocol for the detection of parathyroid adenomas. We manage to obtain a multitude of phases, allowing for a dynamic evaluation within an acceptable exposure range when compared to classic helical 4DCT. Our 4DCT protocol may allow for a better visualization of the pattern of enhancement of parathyroid lesions, as enhancement over time curves can be drawn. This way wash-in and wash-out of contrast in suspected lesions can be readily demonstrated. Motion artifacts are less problematic as multiple phases are available.


2020 ◽  
Vol 19 (1) ◽  
pp. 53-60
Author(s):  
N. P. Tkachuk ◽  
I. S. Davydenko

In spite of a considerable efficacy of conservative treatment of goiter, surgery remains the main method of treatment of such patients. Though, on the one hand, total thyroidectomy inevitably results in the development of postsurgical hypothyroidism, on the other hand – in case organ-saving surgery is performed the risk of postsurgical relapse arises. Modern morphological methods are directed to detection of oncological risk of nodular formations, and recommendations concerning an adequate volume of surgery taking into account probability of relapse are practically lacking. Therefore, the objective of the study was finding criteria of a relapsing risk by means of investigation of morphological peculiarities of the parenchymal-stromal correlations in the thyroid gland with recurrent nodular and primary nodular (multinodular) goiter without signs of functional disorders. In the course of the research according to the examined correlation parameters of the parenchyma and stroma various forms of nodular goiter were found to differ from the thyroid tissue without pathological changes by a number of parameters. In particular, specific weight of the parenchyma on an average increases reliably in the tissue of nodular goiter with its various variants in comparison with the thyroid gland without pathological changes. Together with the increase of the parenchymal specific weight in nodular goiter the amount of colloid on an average decreases, and a specific dependence on the kind of goiter is observed – colloid volume decreases from goiter with slow growth to goiter with quick growth, and it is the smallest with goiter relapse. Quantitative analysis of the goiter tissue stromal component demonstrates a considerable increase of its specific volume in comparison with normal thyroid tissue. Evaluation of changes of the morphometric parameters in the thyroid follicles found that in case of nodular goiter with slow growth the percentage of follicles with colloid is close to 100%. On an average it does not differ from that of the normal thyroid tissue. At the same time, in case of nodular goiter with quick growth the percentage of follicles with colloid decreases sharply, and in case of relapse it appears to be still less than that in nodular goiter with quick growth. Besides, with nodular goiter the diameter of follicles on an average increases in comparison with the normal thyroid tissue. In a number of cases it can be estimated as macrofollicular goiter. At the same time, the diameter of follicles is smaller in nodular goiter with quick growth. It is still less in case of goiter relapse. The size of follicles becomes sharply diverse in case of nodular goiter with slow growth, but it decreases in case of nodular goiter with quick growth and relapse. Consequently, recurrent nodular goiter is mostly similar to that of primary nodular goiter with a quick growth, though certain differences between them exist. The peculiarities found enable to suggest that nodular goiter with a quick growth possesses more chances for relapse.


Sign in / Sign up

Export Citation Format

Share Document