scholarly journals An efficient method to detect calcitonin mRNA in normal and neoplastic rat C-cells (medullary thyroid carcinoma) by in situ hybridization using a digoxigenin-labeled synthetic oligodeoxyribonucleotide probe.

1993 ◽  
Vol 41 (3) ◽  
pp. 389-395 ◽  
Author(s):  
P Le Guellec ◽  
S Dumas ◽  
G E Volle ◽  
E Pidoux ◽  
M S Moukhtar ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Thyroid Carcinoma ◽  
Tumor Cells ◽  
Medullary Thyroid Carcinoma ◽  
Secretory Process ◽  
Blue Color ◽  
C Cells ◽  
Mature Peptide ◽  
Medullary Thyroid

We report here an efficient and rapid method for the specific detection of calcitonin in tumor C-cells of medullary thyroid carcinoma (MTC). This occasionally aggressive tumor arises from the endocrine thyroid C-cells. Its principal marker is calcitonin, the predominant C-cell secretion, which is detected in patients and in our animal model by radioimmunoassay of the plasma, as well as by immunohistochemistry of thyroid tissues. Although calcitonin is easily detectable in normal C-cells, its content is greatly reduced in tumor cells owing to the disappearance of the secretory granules that store the mature peptide. This finding suggests cell dedifferentiation correlated with an increasing aggressivity of the tumor. We therefore developed a rapid detection of calcitonin mRNA by in situ hybridization on routine paraffin sections, using a synthetic oligodeoxyribonucleotide probe labeled with digoxigenin-dUTP. The reaction was detected with an anti-digoxigenin antibody conjugated with alkaline phosphatase, and the enzyme catalyzed the appearance of a dark blue color. The signal was exclusively restricted to the normal, hyperplastic, and tumor C-cells. It was specific, as increasing concentrations of the unlabeled oligonucleotide led to progressive disappearance of the reaction. Its sensitivity was slightly diminished as compared with corresponding frozen sections, but the intensity of the signal was quite acceptable. High levels of calcitonin mRNA were found in all normal and hyperplastic C-cells. They were increased in most of the tumor MTC cells, which did not correlate with the amount of intracellular peptide stores but explained the abnormally high basal levels of circulating calcitonin of the tumor-bearing rats. ISH is therefore of greater value than ICC for an early anatomopathological detection of this tumor. Our data show that the tumor cells are not "dedifferentiated." They only lack the granular compartment storing the mature peptide before exocytosis, but CT biosynthesis and the rest of the secretory process seem to be complete. Our results suggest that factors expressed in malignant C-cells affect basic cell mechanisms involved in the storage of the mature calcitonin, rather than the expression of the CALC gene.

scholarly journals Cushing’s Syndrome Due to Medullary Thyroid Carcinoma: Diagnosis by Proopiomelanocortin Messenger Ribonucleic Acid in Situ Hybridization

2003 ◽  
Vol 88 (10) ◽  
pp. 4565-4568 ◽  
Author(s):  
R. C. Smallridge ◽  
K. Bourne ◽  
B. W. Pearson ◽  
J. A. van Heerden ◽  
P. C. Carpenter ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Thyroid Carcinoma ◽  
Neck Dissection ◽  
Medullary Thyroid Carcinoma ◽  
Cushing's Syndrome ◽  
Plasma Acth ◽  
Mri Scan ◽  
Ectopic Acth ◽  
Medullary Thyroid

Abstract Medullary thyroid carcinoma (MTC) rarely causes ectopic ACTH syndrome. We describe a 38-yr-old man with renal stones who had a 5-cm MTC removed in 1992. He was RET-protooncogene positive (codon 618). Serum calcitonin was 1597 pg/ml postoperatively. In 1996 he had rib fractures, bruising, weakness, and three to four stools per day. Laboratory studies revealed an elevated 24-h urine-free cortisol (780 μg/d), epinephrine (66 μg/d), and calcium (558 mg/d). Baseline serum cortisol was 23.9 μg/dl and decreased to 12.9 and 4.5 μg/dl after 2 mg and 8 mg dexamethasone suppression, respectively. Plasma ACTH was 170 pg/ml and decreased to 75 and 24 pg/ml after dexamethasone. Bone density t-score was −4.3 (trochanter). Computed tomography scans showed multiple cervical nodes and 2-cm right adrenal nodule. Magnetic resonance imaging (MRI) scan showed a prominent, homogeneous pituitary; the adrenal MRI scan was not typical for a pheochromocytoma. Serum CRH was less than 6.6 pg/ml. Bilateral adrenalectomy revealed two adjacent right adrenal pheochromocytomas and corrected the elevated urine cortisol (30 μg/d), epinephrine (0 μg/d), and calcium (281 mg/d) but not plasma ACTH (125 pg/ml). Neck dissection reduced calcitonin by 96% (5300 to 120 pg/ml) and ACTH by 91% (125 to 11 pg/ml). Carcinoembryonic antigen was reduced from 32.0 to 2.3 ng/ml. Immunohistochemical stain was negative for ACTH in the MTC-positive lymph nodes and the pheochromocytoma. Proopiomelanocortin mRNA by in situ hybridization was positive in the MTC but not in the pheochromocytoma. A repeat pituitary MRI scan was normal. The differential diagnosis of ACTH-dependent Cushing’s syndrome in this case included pituitary disease or ectopic ACTH, either from medullary thyroid carcinoma or pheochromocytoma. ACTH stains were unrevealing, but proopiomelanocortin mRNA in situ hybridization in MTC tissue and plasma ACTH response to neck dissection confirmed MTC as the source of ectopic ACTH.

scholarly journals A Review of the Significance in Measuring Preoperative and Postoperative Carcinoembryonic Antigen (CEA) Values in Patients with Medullary Thyroid Carcinoma (MTC)

Medicina ◽  
2021 ◽  
Vol 57 (6) ◽  
pp. 609
Author(s):  
Ioannis Passos ◽  
Elisavet Stefanidou ◽  
Soultana Meditskou-Eythymiadou ◽  
Maria Mironidou-Tzouveleki ◽  
Vasiliki Manaki ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Carcinoembryonic Antigen ◽  
Medullary Thyroid Carcinoma ◽  
Clinical Significance ◽  
Relevant Literature ◽  
Distant Metastases ◽  
Lymph Node Involvement ◽  
C Cells ◽  
Gastrointestinal Malignancies ◽  
Medullary Thyroid

Background and Objectives: Medullary thyroid carcinoma (MTC) accounts for 1–2% of all thyroid malignancies, and it originates from parafollicular “C” cells. Carcinoembryonic antigen (CEA) is a tumor marker, mainly for gastrointestinal malignancies. There are references in literature where elevated CEA levels may be the first finding in MTC. The aim of this study is to determine the importance of measuring preoperative and postoperative CEA values in patients with MTC and to define the clinical significance of the correlation between CEA and the origin of C cells. Materials and Methods: The existing and relevant literature was reviewed by searching for articles and specific keywords in the scientific databases of PubMedCentraland Google Scholar (till December 2020). Results: CEA has found its place, especially at the preoperative level, in the diagnostic approach of MTC. Preoperative CEA values >30 ng/mL indicate extra-thyroid disease, while CEA values >100 ng/mL are associated with lymph node involvement and distant metastases. The increase in CEA values preoperatively is associated with larger size of primary tumor, presence of lymph nodes, distant metastases and a poorer prognosis. The clinical significance of CEA values for the surgeon is the optimal planning of surgical treatment. In the recent literature, C cells seem to originate from the endoderm of the primitive anterior gut at the ultimobranchial bodies’ level. Conclusions: Although CEA is not a specific biomarker of the disease in MTC, itsmeasurement is useful in assessing the progression of the disease. The embryonic origin of C cells could explain the increased CEA values in MTC.

Expression of laminin-2 by normal and neoplastic rat C cells during the development of medullary thyroid carcinoma

1999 ◽  
Vol 434 (4) ◽  
pp. 325-332 ◽  
Author(s):  
Fatima Lekmine ◽  
Hélène Feracci ◽  
Gérard Milhaud ◽  
Françoise Treilhou-Lahille ◽  
N. Jeanne
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
C Cells ◽  
Medullary Thyroid

Medullary thyroid carcinoma

2011 ◽  
pp. 625-630
Author(s):  
Friedhelm Raue ◽  
Karin Frank-Raue
Keyword(s):  
Sex Ratio ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Hereditary Disease ◽  
C Cells ◽  
Biochemical Screening ◽  
Medullary Thyroid ◽  
Histological Features ◽  
Sporadic Disease ◽  
Male To Female

Medullary thyroid carcinoma (MTC) is a rare calcitonin-secreting tumour of the parafollicular or C cells of the thyroid. As the C cells originate from the embryonic neural crest, MTC often have the clinical and histological features of neuroendocrine tumours. They account for 8–12% of all thyroid carcinomas and occur in both sporadic and hereditary forms (1). The majority of patients have sporadic MTC (70%), while 30% have hereditary MTC. The sex ratio in sporadic MTC is 1:1.3 (male to female), while both sexes are nearly equally affected in the familial variety (2). The highest incidence of sporadic disease occurs in the fifth decade of life, while hereditary disease can be diagnosed earlier, depending on the possibility of genetic and biochemical screening.

scholarly journals Expression and role of estrogen receptor α and β in medullary thyroid carcinoma: different roles in cancer growth and apoptosis

2007 ◽  
Vol 195 (2) ◽  
pp. 255-263 ◽  
Author(s):  
Mi Ae Cho ◽  
Mi Kyung Lee ◽  
Kee-Hyun Nam ◽  
Woung Youn Chung ◽  
Cheong Soo Park ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Tumor Staging ◽  
Estrogen Receptor Α ◽  
C Cells ◽  
Tissue Samples ◽  
Medullary Thyroid ◽  
Tt Cells

Medullary thyroid carcinoma (MTC) originates from parafollicular C cells. Estrogen receptor β(ERβ) expressionwas detected in normal parafollicular C cells and MTC tumor tissue, but ERα expression in MTC tumors still remains undetermined. The appearance and loss of ERα or ERβ expression has been known to play a role in the development and progression of many human cancers. We performed immunohistochemical studies of ERα, ERβ, and Ki67, a mitotic index, in 11 human MTC tissue samples. ERα was detected in 10 cases (91%), and ERβ expression was observed in 8 cases (72.7%). A majority (8/10) of ERα-positive tumors showing ERβ Ki67 expression was detected in three cases (27.3%). Neither clinical parameters nor tumor node metastasis (TNM) tumor staging was correlated with the positivity for ERs or Ki67. To investigate the biological role of each ER, we used ER-negative MTC TT cells and adenoviral vectors carrying ERα (Ad-ERα), ERβ (Ad-ERβ), estrogen response element (ERE)-Luc (Ad-ERE-Luc), and activator protein 1 (AP1)-Luc (Ad-AP1-Luc). Estrogen stimulated and anti-estrogen, ICI 182 780, suppressed ERE reporter activity in TT cells expressing ERα or ERβ, suggesting that both ERs use the same classical ERE-mediated pathway. Ad-ERα infection stimulated TT cell growth; in contrast, Ad-ERβ infection suppressed their growth. Apoptosis was detected in Ad-ERβ-infected TT cells. Estrogen and anti-estrogen suppressed AP1 activity in Ad-ERα-infected cells, whereas upon Ad-ERβ infection estrogen further stimulated AP1 activity which in turn is suppressed by anti-estrogen, suggesting that each ER acts differently through a non-ERE-mediated pathway. Our results suggest that ERα and ERβ may play different roles in MTC tumor growth and progression.

scholarly journals Molecular genetics of medullary thyroid carcinoma: the quest for novel therapeutic targets

2009 ◽  
Vol 43 (4) ◽  
pp. 143-155 ◽  
Author(s):  
Aniello Cerrato ◽  
Valentina De Falco ◽  
Massimo Santoro
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Therapeutic Targets ◽  
C Cells ◽  
Rare Tumour ◽  
Medullary Thyroid ◽  
Early Evidence ◽  
Molecular Therapeutic ◽  
Molecular Therapeutic Targets ◽  
Novel Therapeutic

Medullary thyroid carcinoma (MTC) is a rare tumour arising from neural crest-derived parafollicular C-cells. Metastatic MTC patients are incurable because the cancer does not respond to radiotherapy or chemotherapy. The REarranged during Transfection (RET) proto-oncogene plays a key role in the development of MTC. However, one-half of the sporadic MTC do not carry RET mutations. Mice models and early evidence obtained in human samples suggest that other genes, including those encoding components of the RB1 (retinoblastoma) and TP53 tumour-suppressor pathways, may be involved in MTC formation. Here, we review the data on the involvement of genes acting in the RET and RB1/TP53 pathways in MTC. Understanding genetic lesions that occur in MTC is a prerequisite to identifying molecular therapeutic targets in MTC and in improving the efficacy of RET-targeted therapies.

Establishment of a continuous somatostatin-producing line of medullary thyroid carcinoma cells from BALB/c mice

1986 ◽  
Vol 110 (2) ◽  
pp. 309-NP ◽  
Author(s):  
A. S. Tischler ◽  
Y. C. Lee ◽  
D. Costopoulos ◽  
G. Nunnemacher ◽  
R. A. DeLellis ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Cell Biology ◽  
Culture Medium ◽  
Carcinoma Cells ◽  
C Cells ◽  
Medullary Thyroid ◽  
Transplantable Tumour ◽  
Somatostatin Immunoreactivity ◽  
Somatostatin 14

ABSTRACT A continuous line of somatostatin-producing medullary thyroid carcinoma cells was established from a transplantable tumour in BALB/c mice. Virtually all of the somatostatin immunoreactivity co-chromatographed with somatostatin 14. The tumour cells replicated in spinner cultures with a doubling time of approximately 4 days, and the concentration of somatostatin released into the culture medium increased in proportion to the number of cells. Two-to threefold increases in amounts of stored and released somatostatin were observed after treatment of the cells with bromodeoxyuridine. This cell line might be valuable for studies of somatostatin regulation in normal and neoplastic C-cells, and for other studies of C-cell biology which require a mouse model. J. Endocr. (1986) 110, 309–313

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