Medullary Thyroid Carcinoma Research Articles

Medullary thyroid carcinoma - a 22-year case series from a tertiary hospital center

Medullary thyroid carcinoma - a 22-year case series from a tertiary hospital center

Simultaneous papillary and medullary thyroid carcinoma, primary hyperparathyroidism and ACTH-independent Cushing syndrome- an intriguing puzzle of endocrine disorders

Simultaneous papillary and medullary thyroid carcinoma, primary hyperparathyroidism and ACTH-independent Cushing syndrome- an intriguing puzzle of endocrine disorders

Filamin A is required for RET expression and signaling in medullary thyroid carcinoma (MTC) cells

Filamin A is required for RET expression and signaling in medullary thyroid carcinoma (MTC) cells

New plasma biomarkers: XIAP and survivin in patients with medullary thyroid cancer (MTC)

New plasma biomarkers: XIAP and survivin in patients with medullary thyroid cancer (MTC)

Medullary thyroid cancer: case series presentation

Medullary thyroid cancer: case series presentation

Clinical case of a combination of giant prolactinoma and medullary thyroid cancer

Clinical case of a combination of giant prolactinoma and medullary thyroid cancer

Clinical presentation of sporadic and familial medullary thyroid carcinoma: is there a real difference?

Clinical presentation of sporadic and familial medullary thyroid carcinoma: is there a real difference?

Time Kinetics and prognosis roles of calcitonin after surgery for medullary thyroid carcinoma

BackgroundMedullary thyroid carcinoma (MTC) is a malignant tumor with low incidence. Currently, most studies have focused on the prognostic risk factors of MTC, whatever, time kinetic and risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) are yet to be elucidated.MethodsA retrospective study was conducted for 190 MTC patients. Risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) were analyzed. The predictors of calcitonin normalization time (CNT) and biochemical persistent/recurrent time (BPT) were identified. Further, the prognostic roles of CNT and BPT were also demonstrated.ResultsThe 5- and 10-year DFS were 86.7% and 70.2%, respectively. The 5- and 10-year OS were 97.6% and 78.8%, respectively. CN was achieved in 120 (63.2%) patients, whereas BP was presented in 76 (40.0%) patients at the last follow up. After curative surgery, 39 (32.5%) and 106 (88.3%) patients achieved CN within 1 week and 1 month. All patients who failed to achieve CN turned to BP over time and 32/70 of them developed structural recurrence. The median time of CNT and BPT was 1 month (1 day to 84 months) and 6 month (3 day to 63months), respectively. LNR > 0.23 and male gender were independent predictors for CN and BP. LNR > 0.23 (Hazard ratio (HR), 0.24; 95% CI,0.13–0.46; P < 0.01) and male gender (HR, 0.65; 95% CI, 0.42–0.99; P = 0.045) were independent predictors for longer CNT. LNR > 0.23 (HR,5.10; 95% CI,2.15–12.11; P < 0.01) was still the strongest independent predictor followed by preoperative serum Ctn > 1400ng/L (HR,2.34; 95% CI,1.29–4.25; P = 0.005) for shorter BPT. In survival analysis, primary tumor size > 2 cm (HR, 5.81; 95% CI,2.20-15.38; P < 0.01), CNT > 1 month (HR, 5.69; 95% CI, 1.17–27.61; P = 0.031) and multifocality (HR, 3.10; 95% CI, 1.45–6.65; P = 0.004) were independent predictor of DFS.ConclusionEarly changes of Ctn after curative surgery can predict the long-term risks of biochemical and structural recurrence, which provide a useful real-time prognostic information. LNR significantly affect the time kinetic of biochemical prognosis. Tumor burden and CNT play a crucial role in MTC survival, the intensity of follow-up must be tailored accordingly.

Basal calcitonin and calcium gluconate test in suspect medullary thyroid carcinoma: Are we expecting too much from stimulated calcitonin?

Basal calcitonin and calcium gluconate test in suspect medullary thyroid carcinoma: Are we expecting too much from stimulated calcitonin?

Molecular characterization of circulating tumor cells (CTCs) in sporadic medullary thyroid carcinoma (spMTC) patients

Molecular characterization of circulating tumor cells (CTCs) in sporadic medullary thyroid carcinoma (spMTC) patients

Medullary thyroid carcinoma presenting with carcinoid syndrome: a case report

Medullary thyroid carcinoma presenting with carcinoid syndrome: a case report

Dazzeling evolution with unusual metastases of a medullary thyroid carcinoma: about a case

Dazzeling evolution with unusual metastases of a medullary thyroid carcinoma: about a case

Spontaneous and treatment-related changes in calcitonin doubling rate of medullary thyroid cancer. Long-term experience in a patient with multiple endocrine neoplasia type 2B

Spontaneous and treatment-related changes in calcitonin doubling rate of medullary thyroid cancer. Long-term experience in a patient with multiple endocrine neoplasia type 2B

Challenges and pitfalls in the management of medullary thyroid cancer - Real-life data from a tertiary center in Romania

Challenges and pitfalls in the management of medullary thyroid cancer - Real-life data from a tertiary center in Romania

A rare case of encapsulated medullary thyroid cancer

A rare case of encapsulated medullary thyroid cancer

Diagnosis and therapy of medullary thyroid cancer. A real-life, retrospective, multicentric, Hungarian study

Diagnosis and therapy of medullary thyroid cancer. A real-life, retrospective, multicentric, Hungarian study

Clinical and histopathological factors associated with the prognosis of medullary thyroid cancer in a tertiary center

Clinical and histopathological factors associated with the prognosis of medullary thyroid cancer in a tertiary center

LINC00887 Acts as an Enhancer RNA to Promote Medullary Thyroid Carcinoma Progression by Binding with FOXQ1.

Medullary thyroid carcinoma (MTC) is a rare but aggressive endocrine malignancy that originates from the parafollicular C cells of the thyroid gland. Enhancer RNAs (eRNAs) are non-coding RNAs transcribed from enhancer regions, which are critical regulators of tumorigenesis. However, the roles and regulatory mechanisms of eRNAs in MTC remain poorly understood. This study aims to identify key eRNAs regulating the malignant phenotype of MTC and to uncover transcription factors involved in the regulation of key eRNAs. GSE32662 and GSE114068 were used for the identification of differentially expressed genes, eRNAs, enhancers and enhancer-regulated genes in MTC. Metascape and the transcription factor affinity prediction method were used for gene function enrichment and transcription factor prediction, respectively. qRT-PCR was used to detect gene transcription levels. ChIP-qPCR was used to assess the binding of histone H3 lysine 27 acetylation (H3K27ac)-enriched regions to anti- H3K27ac. RIP-qPCR was used to detect the binding between FOXQ1 and LINC00887. CCK8 and Transwell were performed to measure the proliferation and invasion of MTC cells, respectively. Intracellular reactive oxygen species (ROS) levels were quantified using a ROS assay kit. Four eRNAs (H1FX-AS1, LINC00887, MCM3AP-AS1 and A1BG-AS1) were screened, among which LINC00887 was the key eRNA promoting the proliferation and invasion of MTC cells. A total of 135 genes controlled by LINC00887-regulated enhancers were identified; among them, BCL2, PRDX1, SFTPD, TPO, GSS, RAD52, ZNF580, and ZFP36L1 were significantly enriched in the "ROS metabolic process" term. As a transcription factor regulating genes enriched in the "ROS metabolic process" term, FOXQ1 could recruit LINC00887. Overexpression of FOXQ1 restored LINC00887 knockdown-induced downregulation of GSS and ZFP36L1 transcription in MTC cells. Additionally, FOXQ1 overexpression counteracted the inhibitory effects of LINC00887 knockdown on the proliferation and invasion of MTC cells and the promotion of intracellular ROS accumulation induced by LINC00887 knockdown. LINC00887 was identified as a key eRNA promoting the malignant phenotype of MTC cells. The involvement of FOXQ1 was essential for LINC00887 to play a pro-tumorigenic role in MTC. Our findings suggest that the FOXQ1/LINC00887 axis is a potential therapeutic target for MTC.

RET Alterations Differentiate Molecular Profile of Medullary Thyroid Cancer.

Medullary thyroid cancer (MTC) is a rare cancer originating from parafollicular C cells of the thyroid gland. Therapeutically relevant alterations in MTC are predominantly reported in RET oncogene, and lower-frequency alterations are reported in KRAS and BRAF. Nevertheless, there is an unmet need existing to analyze the MTC in the Indian cohort by using in-depth sequencing techniques that go beyond the identification of known therapeutic biomarkers. Here, we characterize MTC using integrative whole-exome and whole-transcriptome sequencing of 32 MTC tissue samples. We performed clinically relevant variant analysis, molecular pathway analysis, tumor immune-microenvironment analysis, and structural characterization of RET novel mutation. Mutational landscape analysis shows expected RET mutations in 50% of the cases. Furthermore, we observed mutations in known cancer genes like KRAS, HRAS, SF3B1, and BRAF to be altered only in the RET-negative cohort. Pathway analysis showed differential enrichment of mutations in transcriptional deregulation genes in the RET-negative cohort. Furthermore, we observed novel RET kinase domain mutation Y900S showing affinity to RET inhibitors accessed via molecular docking and molecular dynamics simulation. Altogether, this study provides a detailed genomic characterization of patients with MTC of Indian origin, highlighting the possible utility of targeted therapies in this disease.

Spontaneous and Treatment-Related Changes of Serum Calcitonin in Medullary Thyroid Cancer: Long-Term Experience in a Patient With Multiple Endocrine Neoplasia Type 2B.

Medullary thyroid carcinoma (MTC) in MEN2B syndrome is associated with germline RET mutation. Patients harboring de novo mutations are usually diagnosed at more advanced disease stages. We present a young woman with Met918Th mutation diagnosed with stage IV MTC at age 10 years. The disease progressed despite total thyroidectomy and multiple surgical interventions for cervical lymph node recurrences, leading to distant metastases in the fifth year after the initial diagnosis. Subsequently, she underwent five different types of tyrosine kinase inhibitor (TKI) treatments. The 17-year disease course was divided into periods defined by four surgical interventions and sequential treatment intervals with four multikinase (sunitinib, vandetanib, cabozantinib, and lenvatinib) and one RET-selective TKI (selpercatinib). Tumor growth for different phases of spontaneous development and drug treatment intervals was characterized by changes in serial log-transformed calcitonin measurements (n = 114). Three operations (one for calcitonin-producing adrenal pheochromocytoma) were associated with drops in calcitonin levels. All of the nonselective TKIs were stopped due to adverse effects. As reflected by the negative calcitonin doubling rate, the best treatment response was observed with selpercatinib, which was associated with an initial large drop followed by a decreasing calcitonin trajectory over 514 days without any major side effects. This case of MEN2B medullary thyroid cancer with long-term survival presents how the effectiveness of different treatment modalities can be estimated using log-transformed calcitonin levels. Furthermore, our experience supports the view that serial calcitonin measurements may be more sensitive than radiological follow-up in advanced MTC. Our patient also represents a new case of rarely reported calcitonin-producing pheochromocytomas.