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International Journal of Surgery... May 2017Medullary thyroid carcinoma (MTC) represents 3-5% of thyroid cancers. 75% is sporadic and 25% is the dominant component of the hereditary multiple endocrine neoplasia... (Review)
Review
UNLABELLED
Medullary thyroid carcinoma (MTC) represents 3-5% of thyroid cancers. 75% is sporadic and 25% is the dominant component of the hereditary multiple endocrine neoplasia (MEN) type 2 syndromes. Three different subtypes of MEN2, such as MEN2A, MEN2B, and Familial MTC (FMTC) have been defined, based on presence or absence of hyperparathyroidism, pheocromocytoma and characteristic clinical features. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC, but there are many other mutational patterns involved. In MEN2A, Codon 634 in exon 11 (Cys634Arg), corresponding to a cysteine in the extracellular cysteine-rich domain, is the most commonly altered codon. Many other mutations include codons 611, 618, 620. In the genetical testing of RET mutations in MTCs, Next-Generation Sequencing (NGS) is taking an increasingly important role. One of the most important benefit is the comprehensive analysis of molecular alterations in MTC, which allows rapidly to select patients with different risk levels. There is a difference in miRNA expression pathway between sporadic and hereditary MTCs. Among sporadic cases, expression of miR-127 was significantly lower in those who harbor somatic RET mutations than those with wild-type RET. CDKN1B mutations are associated with many clinical pictures of cancers, such as MEN4. V109G polymorphism is associated with sporadic MTCs negative for RET mutations, and might influence the clinical course of the patients affected by MTC. Although surgery (i.e. total thyroidectomy with neck lymph node dissection) is the elective treatment for MTCs, about 80% of patients have distant metastases at diagnosis and in this cases surgery is not enough and an additional treatment is needed. Interesting results come from two large phase III clinical trials with two targeted tyrosine kinase inhibitors (TKIs), vandetanib and cabozantinib.
CONCLUSIONS
New genetical testings and therapeutical approaches open new perspectives in MTC management.
Topics: Anilides; Carcinoma, Medullary; Codon; Exons; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia Type 2a; Mutation; Piperidines; Polymorphism, Genetic; Proto-Oncogene Mas; Proto-Oncogene Proteins c-ret; Pyridines; Quinazolines; Thyroid Neoplasms; Thyroidectomy
PubMed: 28506408
DOI: 10.1016/j.ijsu.2017.02.064 -
The Journal of Clinical Endocrinology... Sep 2023Management of sporadic medullary thyroid microcarcinoma smaller than 1 cm (micro-MTC) is controversial because of conflicting reports of prognosis. As these cancers are...
CONTEXT
Management of sporadic medullary thyroid microcarcinoma smaller than 1 cm (micro-MTC) is controversial because of conflicting reports of prognosis. As these cancers are often diagnosed incidentally, they pose a management challenge when deciding on further treatment and follow-up.
OBJECTIVE
We report the outcomes of surgically managed sporadic micro-MTC in a specialist endocrine surgery and endocrinology unit and identify associations for recurrence and disease-specific survival in this population.
METHODS
Micro-MTCs were identified from a prospectively maintained surgery database, and slides were reviewed to determine pathological grade. The primary end points were recurrence, time to recurrence and disease-specific survival. Prognostic factors assessed included size, grade, lymph node metastasis (LNM), and postoperative calcitonin.
RESULTS
From 1995 to 2022, 64 patients were diagnosed with micro-MTC with 22 excluded because of hereditary disease. The included patients had a median age of 60 years, tumor size of 4 mm, and 28 (67%) were female. The diagnosis was incidental in 36 (86%) with 4 (10%) being high grade, 5 (12%) having LNM and 9 (21%) having elevated postoperative calcitonin. Over a 6.6-year median follow-up, 5 (12%) developed recurrence and 3 (7%) died of MTC. High grade and LNM were associated with 10-year survival estimates of 75% vs 100% for low grade and no LNM (hazard ratio = 831; P < .01). High grade, LNM, and increased calcitonin were associated with recurrence (P < .01). Tumor size and type of surgery were not statistically significantly associated with recurrence or survival. No patients with low grade micro-MTC and normal postoperative calcitonin developed recurrence.
CONCLUSION
Most sporadic micro-MTCs are detected incidentally and are generally associated with good outcomes. Size is not significantly associated with outcomes. Using grade, LNM, and postoperative calcitonin allows for the identification of patients at risk of recurrence to personalize management.
Topics: Humans; Female; Middle Aged; Male; Calcitonin; Thyroid Neoplasms; Thyroidectomy; Lymph Node Excision; Carcinoma, Medullary; Prognosis; Peptide Hormones; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Retrospective Studies
PubMed: 36964913
DOI: 10.1210/clinem/dgad173 -
The American Journal of Surgical... Jul 2014
Topics: Biomarkers, Tumor; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Kidney Medulla; Kidney Neoplasms; Kidney Tubules, Collecting; Neoplasm Grading; Predictive Value of Tests; Prognosis; Terminology as Topic
PubMed: 24805860
DOI: 10.1097/PAS.0000000000000222 -
Frontiers in Endocrinology 2021Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor that accounts for 2-4% of all thyroid cancers. All inherited MTC and approximately 50% of sporadic cases... (Review)
Review
Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor that accounts for 2-4% of all thyroid cancers. All inherited MTC and approximately 50% of sporadic cases are driven by mutations in the arranged during ransfection ( proto-oncogene. The recent expansion of the armamentarium of RET-targeting tyrosine kinase inhibitors (TKIs) has provided effective options for systemic therapy for patients with metastatic and progressive disease. However, patients that develop resistant disease as well as those with other molecular drivers such as RAS have limited options. An improved understanding of mechanisms of resistance to TKIs as well as identification of novel therapeutic targets is needed to improve outcomes for patients with MTC.
Topics: Animals; Antineoplastic Agents; Biomarkers, Tumor; Carcinoma, Neuroendocrine; Humans; Molecular Targeted Therapy; Thyroid Neoplasms
PubMed: 34489865
DOI: 10.3389/fendo.2021.708949 -
Frontiers in Oncology 2022Medullary thyroid carcinoma (MTC) is one of the common malignant endocrine tumors, which seriously affects human health. Although surgical resection offers a potentially...
Medullary thyroid carcinoma (MTC) is one of the common malignant endocrine tumors, which seriously affects human health. Although surgical resection offers a potentially curative therapeutic option to some MTC patients, most patients do not benefit from it due to the difficulty to access the tumors and tumor metastasis. The survival rate of MTC patients has improved with the recent advances in the research, which has improved our understanding of the molecular mechanism underlying MTC and enabled the development and approval of novel targeted drugs. In this article, we reviewed the molecular mechanisms related to MTC progression and the principle for the design of molecular targeted drugs, and proposed some future directions for prospective studies exploring targeted drugs for MTC.
PubMed: 36544713
DOI: 10.3389/fonc.2022.993725 -
Surgery Sep 2021Unlike medullary thyroid carcinoma in adults, the vast majority of pediatric medullary thyroid carcinoma is hereditary. Pediatric medullary thyroid carcinoma is known to...
BACKGROUND
Unlike medullary thyroid carcinoma in adults, the vast majority of pediatric medullary thyroid carcinoma is hereditary. Pediatric medullary thyroid carcinoma is known to have different genetic alterations driving tumorigenesis, but it is not known if pediatric medullary thyroid carcinoma has different clinicopathologic features. This study aims to identify which pediatric medullary thyroid carcinoma patients might warrant elective neck dissection.
METHODS
We selected all patients ages 0 to 19 diagnosed with clinically evident medullary thyroid carcinoma in the National Cancer Database between 2004 to 2016. Clinicopathologic factors, treatments, and outcomes were analyzed and compared between this cohort and adults (ages ≥20) with medullary thyroid carcinoma.
RESULTS
One hundred twenty-five pediatric medullary thyroid carcinoma (median age: 13) and 5,086 adult medullary thyroid carcinoma (median age: 57) patients were identified. Pediatric patients had smaller tumors (median diameter: 1.2 cm vs 2.0 cm; P < .001), lower rates of nodal metastases (n = 31, 36.9% vs 1,689, 50.4%; P = .02) but double the incidence of multifocal tumors (n = 70, 59.3%, vs 1,412, 29.9%; P < .001) compared with adults. Multifocal tumors conferred a significantly increased risk of nodal metastases in adult medullary thyroid carcinoma (64.4% vs 43.2%; P < .001) but not pediatric medullary thyroid carcinoma (37.7% vs 35.7%; P = .85). Nodal metastases were more frequent among older children (0-5 years: 0.0%, 6-12: 40.7%, 13-19: 41.7%; P = .04). However, rates of occult nodal metastases were similar between older children (6-19 years: n = 12, 21.4%) and adults (557, 25.8% P = .56).
CONCLUSION
Pediatric medullary thyroid carcinoma has lower rates of lymph node metastases compared with adults. The risk of nodal disease was low among the youngest children, but older children ages 6 to 19 were at considerable risk for occult metastases. These findings could guide clinicians in selecting pediatric patients considered for elective lymph node dissection.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma, Neuroendocrine; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Incidence; Infant; Infant, Newborn; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neck Dissection; Retrospective Studies; Thyroid Neoplasms; Thyroidectomy; United States; Young Adult
PubMed: 33838880
DOI: 10.1016/j.surg.2021.03.001 -
Tumour Biology : the Journal of the... Mar 2017We aimed to demonstrate the differences in the expression of glucose metabolism-related proteins according to the thyroid cancer subtypes and investigate the...
We aimed to demonstrate the differences in the expression of glucose metabolism-related proteins according to the thyroid cancer subtypes and investigate the implications of these differences. A total of 566 thyroid cancer patients, including 342 cases of papillary thyroid carcinoma, 112 cases of follicular carcinoma, 70 cases of medullary carcinoma, 23 cases of poorly differentiated carcinoma, 19 cases of anaplastic carcinoma, and 152 cases of follicular adenoma, were enrolled in the study. Immunohistochemical staining for glucose transporter 1, hexokinase II, carbonic anhydrase IX, and monocarbonylate transporter 4 was performed, and the relationship between immunoreactivity and clinicopathologic parameters was analyzed. Glucose transporter 1 and tumoral monocarbonylate transporter 4 expression levels were shown to be the highest in anaplastic carcinoma, and medullary carcinoma showed the highest carbonic anhydrase IX and lowest hexokinase II levels compared with other subtypes. Stromal expression of monocarbonylate transporter 4 was observed in papillary thyroid carcinoma and anaplastic carcinoma samples. Conventional papillary thyroid carcinoma tumors expressed higher levels of glucose transporter 1, and tumoral and stromal monocarbonylate transporter 4, than the follicular variant, which showed a higher expression of carbonic anhydrase IX. Papillary thyroid carcinoma samples with BRAF V600E mutation were shown to have higher glucose transporter 1, hexokinase II, carbonic anhydrase IX, and tumoral monocarbonylate transporter 4 expression levels. Univariate analysis showed that papillary thyroid carcinoma cases with glucose transporter 1 positivity had shorter overall survival, patients with medullary carcinoma and hexokinase II positivity were shown to have a shorter disease-free survival and overall survival, and tumoral monocarbonylate transporter 4 positivity was associated with shorter overall survival compared with papillary thyroid carcinoma patients with negativity for each marker. Disease-free survival and overall survival of patients with poorly differentiated carcinoma were shown to be significantly decreased when glucose transporter 1 and tumoral monocarbonylate transporter 4 are expressed. We demonstrated that the expression levels of glycolysis-related proteins differ between thyroid cancer subtypes and are correlated with poorer prognosis, depending on the subtype.
Topics: Adenocarcinoma, Follicular; Adenoma; Carbonic Anhydrase IX; Carcinoma; Carcinoma, Medullary; Carcinoma, Papillary; Disease-Free Survival; Female; Gene Expression Regulation, Neoplastic; Glucose; Glucose Transporter Type 1; Glycolysis; Hexokinase; Humans; Male; Monocarboxylic Acid Transporters; Muscle Proteins; Thyroid Cancer, Papillary; Thyroid Neoplasms; Tissue Array Analysis
PubMed: 28347233
DOI: 10.1177/1010428317695922 -
Oncology Research 2024This review aimed to describe the inculpation of microRNAs (miRNAs) in thyroid cancer (TC) and its subtypes, mainly medullary thyroid carcinoma (MTC), and to outline... (Review)
Review
This review aimed to describe the inculpation of microRNAs (miRNAs) in thyroid cancer (TC) and its subtypes, mainly medullary thyroid carcinoma (MTC), and to outline web-based tools and databases for bioinformatics analysis of miRNAs in TC. Additionally, the capacity of miRNAs to serve as therapeutic targets and biomarkers in TC management will be discussed. This review is based on a literature search of relevant articles on the role of miRNAs in TC and its subtypes, mainly MTC. Additionally, web-based tools and databases for bioinformatics analysis of miRNAs in TC were identified and described. MiRNAs can perform as oncomiRs or antioncoges, relying on the target mRNAs they regulate. MiRNA replacement therapy using miRNA mimics or antimiRs that aim to suppress the function of certain miRNAs can be applied to correct miRNAs aberrantly expressed in diseases, particularly in cancer. MiRNAs are involved in the modulation of fundamental pathways related to cancer, resembling cell cycle checkpoints and DNA repair pathways. MiRNAs are also rather stable and can reliably be detected in different types of biological materials, rendering them favorable diagnosis and prognosis biomarkers as well. MiRNAs have emerged as promising tools for evaluating medical outcomes in TC and as possible therapeutic targets. The contribution of miRNAs in thyroid cancer, particularly MTC, is an active area of research, and the utility of web applications and databases for the biological data analysis of miRNAs in TC is becoming increasingly important.
Topics: Humans; Thyroid Neoplasms; MicroRNAs; Biomarkers, Tumor; Carcinoma, Neuroendocrine; Prognosis; Computational Biology; Gene Expression Regulation, Neoplastic; Internet; Molecular Targeted Therapy
PubMed: 38827323
DOI: 10.32604/or.2024.049235 -
Cancer Feb 2016Medullary thyroid carcinoma (MTC) is a neuroendocrine malignancy of the thyroid C cells that occurs in hereditary and sporadic clinical settings. Metastatic spread... (Review)
Review
Medullary thyroid carcinoma (MTC) is a neuroendocrine malignancy of the thyroid C cells that occurs in hereditary and sporadic clinical settings. Metastatic spread commonly occurs to cervical and mediastinal lymph nodes. MTC cells do not concentrate radioactive iodine and are not sensitive to hormonal manipulation, and therefore surgery is the most effective option for curative therapy, reduction in tumor burden, or effective palliation. In patients undergoing preventative surgery for hereditary MTC, central lymph node dissection should be considered if the calcitonin level is elevated. Preservation of parathyroid function in these young patients is of paramount importance. In patients with established primary tumors, systematic surgical removal of lymph node basins (compartmental dissection) should be guided by ultrasound mapping of lymph node metastases and level of serum calcitonin. A "berry-picking" approach is discouraged. Newly approved targeted molecular therapies offer wider treatment options for patients with progressive or metastatic disease.
Topics: Biomarkers, Tumor; Calcitonin; Carcinoma, Medullary; Carcinoma, Neuroendocrine; Humans; Lymph Nodes; Lymphatic Metastasis; Molecular Targeted Therapy; Multiple Endocrine Neoplasia Type 2a; Multiple Endocrine Neoplasia Type 2b; Mutation; Neck Dissection; Neoplasm Recurrence, Local; Palliative Care; Prognosis; Proto-Oncogene Proteins c-ret; Reoperation; Thyroid Neoplasms; Thyroidectomy; Ultrasonography
PubMed: 26539937
DOI: 10.1002/cncr.29761 -
Frontiers in Endocrinology 2022Thyroid cancer is the malignant tumor that is increasing most rapidly in the world, mainly at the expense of sporadic papillary thyroid carcinoma. The somatic... (Review)
Review
Thyroid cancer is the malignant tumor that is increasing most rapidly in the world, mainly at the expense of sporadic papillary thyroid carcinoma. The somatic alterations involved in the pathogenesis of sporadic follicular cell derived tumors are well recognized, while the predisposing alterations implicated in hereditary follicular tumors are less well known. Since the genetic background of syndromic familial non-medullary carcinoma has been well established, here we review the pathogenesis of non-syndromic familial non-medullary carcinoma emphasizing those aspects that may be useful in clinical and pathological diagnosis. Non-syndromic familial non-medullary carcinoma has a complex and heterogeneous genetic basis involving several genes and loci with a monogenic or polygenic inheritance model. Most cases are papillary thyroid carcinoma (classic and follicular variant), usually accompanied by benign thyroid nodules (follicular thyroid adenoma and/or multinodular goiter). The possible diagnostic and prognostic usefulness of the changes in the expression and/or translocation of various proteins secondary to several mutations reported in this setting requires further confirmation. Given that non-syndromic familial non-medullary carcinoma and sporadic non-medullary thyroid carcinoma share the same morphology and somatic mutations, the same targeted therapies could be used at present, if necessary, until more specific targeted treatments become available.
Topics: Carcinoma, Medullary; Carcinoma, Neuroendocrine; Humans; Multiple Endocrine Neoplasia Type 2a; Neoplastic Syndromes, Hereditary; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 35295987
DOI: 10.3389/fendo.2022.829103