Quantification of intracellular calcitonin gene transcripts in human medullary thyroid carcinoma (MTC) by in situ hybridization

1990 ◽  
Vol 13 (7) ◽  
pp. 567-573 ◽  
Author(s):  
Michèle Noel ◽  
A. Gavoille ◽  
F. Lasmoles ◽  
E. Kahn ◽  
B. Caillou ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Medullary Thyroid ◽  
Calcitonin Gene ◽  
Gene Transcripts

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.

Detection of calcitonin and calcitonin gene-related peptide mRNA in human medullary thyroid carcinoma. A retrospective study

1993 ◽  
Vol 169 (1) ◽  
pp. 53-60 ◽  
Author(s):  
Maryléne Denijn ◽  
Roel A. De Weger ◽  
Jan A. M. Van Unnik ◽  
Wim Den Otter ◽  
Cees J. M. Lips
Keyword(s):  
Retrospective Study ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Calcitonin Gene Related Peptide ◽  
Medullary Thyroid ◽  
Related Peptide ◽  
Calcitonin Gene

scholarly journals Improved cell-specificity of adeno-associated viral vectors for medullary thyroid carcinoma using calcitonin gene regulatory elements

PLoS ONE ◽  
2020 ◽  
Vol 15 (2) ◽  
pp. e0228005
Author(s):  
Hazel C. Levy ◽  
Danielle Hulvey ◽  
Laura Adamson-Small ◽  
Natacha Jn-Simon ◽  
Victor Prima ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Viral Vectors ◽  
Regulatory Elements ◽  
Medullary Thyroid ◽  
Cell Specificity ◽  
Calcitonin Gene ◽  
Gene Regulatory Elements ◽  
Gene Regulatory
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