Receptors for epidermal growth factor and thyrotropin in thyroid carcinoma

1988 ◽  
Vol 117 (1) ◽  
pp. 45-50 ◽  
Author(s):  
Tuulikki Mäkinen ◽  
Fredrika Pekonen ◽  
Kaarle Franssila ◽  
Bror-Axel Lamberg

Abstract. The EGF and TSH receptor properties in malignant thyroid tumours and adjacent normal thyroid tissues were characterized using radioreceptor assays. Ten patients with papillary, 4 with medullary, 1 with Hürthle cell type follicular carcinoma, and 2 with anaplastic thyroid carcinoma were studied. In 10 out of 12 patients with papillary and anaplastic thyroid carcinomas, more EGF receptors were found in the neoplastic tissue than in the adjacent normal tissue (P < 0.01). The affinity of the EGF receptors varied between patients (from 0.5 × 109 1/mol to 1.9 × 109 1/mol), but was in each patient the same in the neoplastic and in the normal tissue. In medullary carcinomas and a follicular Hiirthle thyroid carcinoma, the EGF receptor content was very low. The receptor number was unaltered or decreased in papillary carcinomas when compared with adjacent normal tissue. In anaplastic medullary and follicular (Hürthle cell) carcinomas, the neoplastic tissue had very few high affinity TSH receptor sites. The alterations in TSH receptor characteristics when thyroid neoplastic tissue was compared with adjacent normal tissue did not correlate to changes in EGF receptor characteristics. Our results demonstrate that the amount of EGF receptors in papillary and anaplastic thyroid carcinomas differ significantly from that in follicular and medullary carcinomas and that alterations in EGF receptor content in malignant thyroid tissues are independent of TSH receptor content.

1987 ◽  
Vol 116 (2) ◽  
pp. 260-266 ◽  
Author(s):  
Noboru Hamada ◽  
Yoshitaka Manabe ◽  
Hifumi Saito ◽  
Takashi Mimura ◽  
Kunihiko Ito

Abstract. The course of the cAMP response to thyrotropin (TSH) in 23 specimens of differentiated thyroid carcinoma and the adjacent normal tissue was studied. In the carcinomatous tissue, the cAMP concentration in slices incubated with TSH was significantly greater after 2 h than after 15 min of incubation; the level was almost the same at both times in normal tissue. The effects of an initial exposure of thyroid slices to TSH (50 U/l on the subsequent cAMP responsiveness to the hormone were investigated in seven more differentiated thyroid carcinomas. In normal tissue, the cAMP level in slices exposed to TSH, washed, and exposed again was lower after the third incubation than in slices exposed to TSH only in the third. In contrast, the cAMP level tended to be greater after the second of 2 TSH incubations in 5 out of the 7 specimens of carcinomatous tissue. The data suggest that differentiated thyroid carcinoma lacks desensitization of the cAMP response to TSH.


Pathobiology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Risa Kanematsu ◽  
Mitsuyoshi Hirokawa ◽  
Aki Tanaka ◽  
Ayana Suzuki ◽  
Miyoko Higuchi ◽  
...  

<b><i>Introduction:</i></b> An immunohistochemical study has occasionally been performed to diagnose anaplastic thyroid carcinoma (ATC). However, antibodies to confirm the undifferentiated nature of ATC have not yet been evaluated. The aim of this study was to evaluate E-cadherin and β-catenin expressions in immunoreactivity to determine undifferentiated carcinoma cells in the diagnosis of ATC. <b><i>Methods:</i></b> We immunohistochemically examined 29 ATCs, 30 poorly differentiated thyroid carcinomas (PDTCs), 22 well-differentiated thyroid carcinomas (WDTCs), and 3 squamous cell carcinomas. Antibodies for thyroid transcription factor-1 (TTF-1), paired-box gene 8 (PAX8), β-catenin, and E-cadherin were used. <b><i>Results:</i></b> All WDTCs tested positive for TTF-1, PAX8, and E-cadherin. The positive rates of TTF-1, PAX8, and E-cadherin were 93.3, 93.3, and 100%, respectively, in PDTCs and 17.2, 51.7, and 10.3%, respectively, in ATCs. WDTC expressed the lateral cell membrane staining for β-catenin and E-cadherin, whereas PDTC showed circumferential cell membranous expression (fishnet pattern). β-catenin cell membrane expression in ATCs is lost or discontinuous. Carcinoma cells with β-catenin nuclear expression without cell membranous expression were scattered in 72.4% of ATCs but were not observed in the other carcinomas. <b><i>Conclusion:</i></b> We propose 3 immunohistochemical findings to determine undifferentiated carcinoma cells in the diagnosis of ATC: (1) β-catenin nuclear expression with no or reduced cell membranous expression, (2) the loss or discontinuous pattern of E-cadherin expression, and (3) the loss of PAX8 nuclear expression.


2011 ◽  
Vol 96 (4) ◽  
pp. 1029-1038 ◽  
Author(s):  
Eleonora Borbone ◽  
Giancarlo Troncone ◽  
Angelo Ferraro ◽  
Zuzana Jasencakova ◽  
Lovorka Stojic ◽  
...  

Abstract Context: Enhancer of zeste homolog 2 (EZH2) is a histone lysine methyltransferase belonging to the polycomb group protein family. Overexpression of EZH2 has been found in several human malignancies including hematological and solid tumors. Objectives: In this study we investigated the expression levels of EZH2 and its polycomb group protein partners in thyroid carcinoma tissues with different degrees of malignancy to identify potential new therapeutic targets for anaplastic thyroid carcinoma (ATC). Results: We show that high EZH2 expression levels are characteristic of undifferentiated ATC, whereas no significant changes were observed in well-differentiated papillary and follicular thyroid carcinomas as compared with normal thyroid. Knockdown of EZH2 in ATC cell lines results in cell growth inhibition, loss of anchorage-independent growth, migration, and invasion properties. Moreover, we demonstrate that EZH2 directly controls differentiation of ATC cells by silencing the thyroid specific transcription factor paired-box gene 8 (PAX8). Conclusions: EZH2 is specifically overexpressed in ATC, and it directly contributes to transcriptional silencing of PAX8 gene and ATC differentiation.


2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Rok Petric ◽  
Barbara Gazic ◽  
Katja Goricar ◽  
Vita Dolzan ◽  
Radan Dzodic ◽  
...  

Background. Hürthle cell thyroid carcinoma (HCTC) is a rare type of thyroid carcinoma. In the present study, we investigated whether the expression of miRNAs of interest is associated with the occurrence of metastases in patients with HCTC.Materials and Methods. In 39 patients with HCTC (22 with nonmetastatic and 17 with regional or distant metastatic disease), the expression levels of six miRNAs (miR-138, miR-183, miR-221, miR-222, miR-768-3p, and miR-885-5p) and U6 snRNA as endogenous control were determined in FFPE samples of primary tumor and normal thyroid tissue using TaqMan miRNA assays.Results. In patients with HCTC, miR-138 and miR-768-3p were downregulated in tumor samples compared to normal tissue (p=0.013andp=0.010, resp.). These two miRNAs were also significantly downregulated in tumor samples of patients with metastatic disease (p=0.030andp=0.048, resp.) but not in patients with nonmetastatic disease (p=0.249andp=0.101, resp.). In patients with nonmetastatic disease, miR-221 and miR-885-5p were slightly, albeit significantly, upregulated in tumorous compared to normal tissue (p=0.042andp=0.027, resp.).Conclusion. Expression of miRNA (miR-183, miR-221, and miR-885-5p) in tumor tissue is associated with the occurrence of distant metastases in patients with HCTC.


2015 ◽  
Vol 100 (4) ◽  
pp. E611-E615 ◽  
Author(s):  
Katayoon Kasaian ◽  
Ana-Maria Chindris ◽  
Sam M. Wiseman ◽  
Karen L. Mungall ◽  
Thomas Zeng ◽  
...  

Context and Objective: Oncocytic thyroid carcinoma, also known as Hürthle cell thyroid carcinoma, accounts for only a small percentage of all thyroid cancers. However, this malignancy often presents at an advanced stage and poses unique challenges to patients and clinicians. Surgical resection of the tumor accompanied in some cases by radioactive iodine treatment, radiation, and chemotherapy are the established modes of therapy. Knowledge of the perturbed oncogenic pathways can provide better understanding of the mechanism of disease and thus opportunities for more effective clinical management. Design and Patients: Initially, two oncocytic thyroid carcinomas and their matched normal tissues were profiled using whole genome sequencing. Subsequently, 72 oncocytic thyroid carcinomas, one cell line, and five Hürthle cell adenomas were examined by targeted sequencing for the presence of mutations in the multiple endocrine neoplasia I (MEN1) gene. Results: Here we report the identification of MEN1 loss-of-function mutations in 4% of patients diagnosed with oncocytic thyroid carcinoma. Whole genome sequence data also revealed large regions of copy number variation encompassing nearly the entire genomes of these tumors. Conclusion: Menin, a ubiquitously expressed nuclear protein, is a well-characterized tumor suppressor whose loss is the cause of MEN1 syndrome. Menin is involved in several major cellular pathways such as regulation of transcription, control of cell cycle, apoptosis, and DNA damage repair pathways. Mutations of this gene in a subset of Hürthle cell tumors point to a potential role for this protein and its associated pathways in thyroid tumorigenesis.


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