scholarly journals Immune Profiling of Medullary Thyroid Cancer—An Opportunity for Immunotherapy

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1534
Author(s):  
Kinga Hińcza-Nowak ◽  
Artur Kowalik ◽  
Agnieszka Walczyk ◽  
Iwona Pałyga ◽  
Danuta Gąsior-Perczak ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Medullary Thyroid Cancer ◽  
Initial Therapy ◽  
Published Data ◽  
Tumor Diameter ◽  
C Cells ◽  
Clinical Factors ◽  
Medullary Thyroid ◽  
Rare Malignancy ◽  
Immune Profiling

Medullary thyroid cancer (MTC) is a rare malignancy that arises from calcitonin-producing C-cells. Curative treatment for patients with metastatic MTC is challenging. Identifying the mechanisms by which cancer cells inhibit the activity of immune cells provides an opportunity to develop new therapies that restore anticancer activity. Little is known about the immunological phenomena underlying MTC. Here, we examined the expression profile of 395 genes associated with MTC. The study included 51 patients diagnosed with MTC at a single center. Bioinformatical analysis revealed that CD276 expression in MTC cells was at least three-fold higher than that in normal tissue. The expression of CD276 showed a weak but statistically significant positive correlation with tumor diameter, but we did not find a significant association between CD276 expression and other histopathological clinical factors, or the response to initial therapy. A search of published data identified the monoclonal antibody (inhibitor) enoblituzumab as a potential drug for patients diagnosed with MTC overexpressing CD276.

Dynamic risk stratification for medullary thyroid cancer according to the response to initial therapy

Endocrine ◽  
2016 ◽  
Vol 53 (1) ◽  
pp. 174-181 ◽  
Author(s):  
Hyemi Kwon ◽  
Won Gu Kim ◽  
Min Ji Jeon ◽  
Dong Eun Song ◽  
Yu-Mi Lee ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Risk Stratification ◽  
Medullary Thyroid Cancer ◽  
Initial Therapy ◽  
Medullary Thyroid ◽  
Dynamic Risk

scholarly journals PROX1 Promotes Secretory Granule Formation in Medullary Thyroid Cancer Cells

Endocrinology ◽  
2016 ◽  
Vol 157 (3) ◽  
pp. 1289-1298 ◽  
Author(s):  
Jun Ishii ◽  
Takuya Yazawa ◽  
Tomohiro Chiba ◽  
Yukiko Shishido-Hara ◽  
Yuu Arimasu ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Papillary Thyroid Cancer ◽  
Secretory Granule ◽  
Chromogranin A ◽  
Medullary Thyroid Cancer ◽  
C Cells ◽  
Papillary Thyroid ◽  
Medullary Thyroid ◽  
Thyroid Cancer Cells

Abstract Mechanisms of endocrine secretory granule (SG) formation in thyroid C cells and medullary thyroid cancer (MTC) cells have not been fully elucidated. Here we directly demonstrated that PROX1, a developmental homeobox gene, is transcriptionally involved in SG formation in MTC, which is derived from C cells. Analyses using gene expression databases on web sites revealed that, among thyroid cancer cells, MTC cells specifically and highly express PROX1 as well as several SG-forming molecule genes. Immunohistochemical analyses showed that in vivo MTC and C cells expressed PROX1, although follicular thyroid cancer and papillary thyroid cancer cells, normal follicular cells did not. Knockdown of PROX1 in an MTC cells reduced SGs detected by electron microscopy, and decreased expression of SG-related genes (chromogranin A, chromogranin B, secretogranin II, secretogranin III, synaptophysin, and carboxypeptidase E). Conversely, the introduction of a PROX1 transgene into a papillary thyroid cancer and anaplastic thyroid cancer cells induced the expression of SG-related genes. Reporter assays using the promoter sequence of chromogranin A showed that PROX1 activates the chromogranin A gene in addition to the known regulatory mechanisms, which are mediated via the cAMP response element binding protein and the repressor element 1-silencing transcription factor. Furthermore, chromatin immunoprecipitation-PCR assays demonstrated that PROX1 binds to the transcriptional regulatory element of the chromogranin A gene. In conclusion, PROX1 is an important regulator of endocrine SG formation in MTC cells.

scholarly journals Comprehensive Immune Profiling of Medullary Thyroid Cancer

Thyroid ◽  
2020 ◽  
Vol 30 (9) ◽  
pp. 1263-1279 ◽  
Author(s):  
Nikita Pozdeyev ◽  
Timothy A. Erickson ◽  
Lian Zhang ◽  
Kim Ellison ◽  
Christopher J. Rivard ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Medullary Thyroid Cancer ◽  
Medullary Thyroid ◽  
Immune Profiling

scholarly journals A BRAF V600E Mutation in RET-Negative Medullary Thyroid Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Richard J. Robbins ◽  
Jessica S. Thomas ◽  
Patricia Mejia Osuna ◽  
Jawairia Shakil
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Cancer ◽  
Genomic Analysis ◽  
Neoplastic Transformation ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
C Cells ◽  
Sporadic Medullary Thyroid Carcinoma ◽  
Medullary Thyroid

We report the case of a woman with a sporadic medullary thyroid carcinoma. Genomic analysis found that her tumor did not contain any common RET mutations but did harbor a BRAF V600E mutation. Only one other well-confirmed example of the BRAF V600E mutation has been reported in an MTC patient. We conclude that this common BRAF mutation may independently drive neoplastic transformation of human parafollicular C cells.

Response to Initial Therapy Predicts Clinical Outcomes in Medullary Thyroid Cancer

Thyroid ◽  
2015 ◽  
Vol 25 (2) ◽  
pp. 242-249 ◽  
Author(s):  
Susan C. Lindsey ◽  
Ian Ganly ◽  
Frank Palmer ◽  
R. Michael Tuttle
Keyword(s):  
Thyroid Cancer ◽  
Clinical Outcomes ◽  
Medullary Thyroid Cancer ◽  
Initial Therapy ◽  
Medullary Thyroid

scholarly journals Medullary Thyroid Cancer Responsiveness to Pentagastrin Stimulation: An Early Surrogate Parameter of Tumor Dissemination?

2008 ◽  
Vol 93 (6) ◽  
pp. 2234-2238 ◽  
Author(s):  
Andreas Machens ◽  
Steffen Hauptmann ◽  
Henning Dralle
Keyword(s):  
Thyroid Cancer ◽  
Lymph Node ◽  
Lymph Node Metastases ◽  
Medullary Thyroid Cancer ◽  
Fold Increase ◽  
Extrathyroidal Extension ◽  
Tumor Diameter ◽  
Medullary Thyroid ◽  
Tumor Dissemination ◽  
Node Metastases

Abstract Context: Because of its outstanding sensitivity, stimulation of calcitonin secretion with iv injection of pentagastrin is widely used for biochemical diagnosis of medullary thyroid cancer. Objective: The objective of this study was to explore the relationship between the results of the pentagastrin stimulation test and extent of disease in patients with previously untreated medullary thyroid cancer. Design: This was a retrospective study. Setting: The investigation took place at a tertiary referral center. Patients: Included were 89 patients with increased basal calcitonin levels who had a pentagastrin test at this institution before initial neck surgery for medullary thyroid cancer. Main Outcome Measure: Measurements included basal and stimulated calcitonin levels, carcinoembryonic antigen levels, primary tumor diameter, extrathyroidal extension, lymph node metastases, and distant metastases. Results: There was a strong dose-dependent relationship between a less than 10-fold increase in preoperative calcitonin levels after iv stimulation with pentagastrin and both the frequency (41–54 vs. 4–27%; P = 0.001) and number (means of 3.0–10.8 vs. 0–1.1 positive nodes, P < 0.001) of lymph node metastases. Weaker associations were identified with the respective frequency of extrathyroidal extension (14–27 vs. 0–7%; P = 0.027), distant metastasis (9–23 vs. 0%; P = 0.017), and postoperative normalization of calcitonin (40–55 vs. 53–82%; P = 0.029). On multivariate analysis, only lymph node metastases were associated with a less than 10-fold increase in preoperative calcitonin levels. Conclusions: Based on these clinical data and preclinical literature, reduced responsiveness to stimulation with pentagastrin may reflect early dedifferentiation. Evidence of this condition may enable early risk stratification in patients with medullary thyroid cancer.

scholarly journals Histopathological and molecular studies in patients with goiter and hypercalcitoninemia: reactive or neoplastic C-cell hyperplasia?

2007 ◽  
Vol 14 (2) ◽  
pp. 393-403 ◽  
Author(s):  
Uberta Verga ◽  
Stefano Ferrero ◽  
Leonardo Vicentini ◽  
Tatiana Brambilla ◽  
Valentina Cirello ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Multinodular Goiter ◽  
Medullary Thyroid Cancer ◽  
Final Diagnosis ◽  
C Cells ◽  
Cell Hyperplasia ◽  
Medullary Thyroid ◽  
C Cell Hyperplasia ◽  
C Cell ◽  
Molecular Studies

The cut-off values able to differentiate between reactive or neoplastic C-cell hyperplasia (CCH) or to predict sporadic medullary thyroid cancer (MTC) are still debated both for basal and stimulated calcitonin (bCT and sCT). In the present study, the prevalence and the histological patterns of CCH in 15 patients with multinodular goiter (MNG), bCT>10 pg/ml and sCT levels >50 pg/ml were studied. As controls, 16 patients with MNG and bCT levels <10 pg/ml and 4 patients with familial (FMTC) were included. For each case, calcitonin (CT) immunoreactive cells were counted in 60 consecutive high-power fields (400×) and CCH classified as focal, diffuse, nodular, or neoplastic. RET genetic analyses were performed at the germline and tissue levels in MTC and CCH cases. In patients with MNG, sCT levels >50 pg/ml were associated with CCH or MTC, being the total number of C-cells/60 fields significantly higher than that found in MNG with normal bCT (P = 0.0008) and comparable with that detected in FMTCs. In the group with sCT>50 pg/ml, the C-cells displayed a neoplastic phenotype. Neither germline nor somatic RET mutations were found. In conclusion, sCT levels >50 pg/ml were always associated with CCH, without correlation between CT levels and the number of C-cells or the final diagnosis. The C-cells had a morphology and distribution pattern similar to those observed in FMTC. Thus, sCT levels >50 pg/ml indicate the presence of CCH with a possible preneoplastic potential, suggesting the opportunity to perform a prophylactic surgical treatment.

Medullary Thyroid Cancer

2018 ◽  
Author(s):  
Geeta Lal
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapies ◽  
Medullary Thyroid Cancer ◽  
Kinase Inhibitors ◽  
The United States ◽  
C Cells ◽  
Medullary Thyroid ◽  
Key Words Genetics ◽  
Thyroid C Cells ◽  
Men 2A

Medullary thyroid cancer (MTC) arises from the thyroid C-cells and accounts for 1 to 2% of thyroid cancers in the United States. Most tumors are sporadic but may occur as a part of the familial syndromes multiple endocrine neoplasia (MEN) 2A, MEN2B, and familial MTC. Surgery is the mainstay of treatment of these tumors, although recent advances in molecular genetics have enabled the development and use of targeted therapies such as tyrosine kinase inhibitors to treat patients with symptomatic metastatic disease.  This review contains 2 figures, 3 tables and 34 references Key Words: genetics, management, medullary thyroid cancer, MEN2A, MEN2B, targeted therapies

Medullary Thyroid Cancer

2018 ◽  
Author(s):  
Geeta Lal
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapies ◽  
Medullary Thyroid Cancer ◽  
Kinase Inhibitors ◽  
The United States ◽  
C Cells ◽  
Medullary Thyroid ◽  
Key Words Genetics ◽  
Thyroid C Cells ◽  
Men 2A

Medullary thyroid cancer (MTC) arises from the thyroid C-cells and accounts for 1 to 2% of thyroid cancers in the United States. Most tumors are sporadic but may occur as a part of the familial syndromes multiple endocrine neoplasia (MEN) 2A, MEN2B, and familial MTC. Surgery is the mainstay of treatment of these tumors, although recent advances in molecular genetics have enabled the development and use of targeted therapies such as tyrosine kinase inhibitors to treat patients with symptomatic metastatic disease.  This review contains 2 figures, 3 tables and 34 references Key Words: genetics, management, medullary thyroid cancer, MEN2A, MEN2B, targeted therapies

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