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JOURNAL ARTICLE
Julius Gudmundsson, Gudmar Thorleifsson, Jon K Sigurdsson, Lilja Stefansdottir, Jon G Jonasson, Sigurjon A Gudjonsson, Daniel F Gudbjartsson, Gisli Masson, Hrefna Johannsdottir, Gisli H Halldorsson, Simon N Stacey, Hannes Helgason, Patrick Sulem, Leigha Senter, Huiling He, Sandya Liyanarachchi, Matthew D Ringel, Esperanza Aguillo, Angeles Panadero, Enrique Prats, Almudena Garcia-Castaño, Ana De Juan, Fernando Rivera, Li Xu, Lambertus A Kiemeney, Gudmundur I Eyjolfsson, Olof Sigurdardottir, Isleifur Olafsson, Hoskuldur Kristvinsson, Romana T Netea-Maier, Thorvaldur Jonsson, Jose I Mayordomo, Theo S Plantinga, Hannes Hjartarson, Jon Hrafnkelsson, Erich M Sturgis, Unnur Thorsteinsdottir, Thorunn Rafnar, Albert de la Chapelle, Kari Stefansson
The great majority of thyroid cancers are of the non-medullary type. Here we report findings from a genome-wide association study of non-medullary thyroid cancer, including in total 3,001 patients and 287,550 controls from five study groups of European descent. Our results yield five novel loci (all with Pcombined <3 × 10-8 ): 1q42.2 (rs12129938 in PCNXL2), 3q26.2 (rs6793295 a missense mutation in LRCC34 near TERC), 5q22.1 (rs73227498 between NREP and EPB41L4A), 10q24.33 (rs7902587 near OBFC1), and two independently associated variants at 15q22...
February 14, 2017: Nature Communications
#22
JOURNAL ARTICLE
Beatriz G Cavalheiro, Leandro L Matos, Ana Kober N Leite, Marco Aurélio V Kulcsar, Claudio R Cernea, Lenine G Brandão
Objective: The aim of the present study was to describe the epidemiologic data, histological type, treatment and follow-up of the 811 patients treated for thyroid cancer in Instituto do Câncer do Estado de São Paulo (ICESP) over 5 years. Materials and methods: Retrospective analyses of electronic chart information. Results: There were 679 cases (83.7%) of papillary thyroid cancer, 61 (7.5%) of follicular carcinoma, 54 (6.7%) of medullary carcinoma, 11 (1...
October 2016: Archives of Endocrinology and Metabolism
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JOURNAL ARTICLE
Jessica Reagh, Martyn Bullock, Juliana Andrici, John Turchini, Loretta Sioson, Adele Clarkson, Nicole Watson, Amy Sheen, Grace Lim, Leigh Delbridge, Stan Sidhu, Mark Sywak, Ahmad Aniss, Phillip Shepherd, Daniel Ng, Paul Oei, Michael Field, Diana Learoyd, Bruce G Robinson, Roderick J Clifton-Bligh, Anthony J Gill
A quarter of patients with medullary thyroid carcinoma (MTC) have germline mutations in the RET proto-oncogene indicating MEN2. Therefore genetic testing is recommended for all patients presenting with MTC. Approximately 40% of MTCs have somatic RET mutations. Somatic mutations in the RAS genes are the next most common driver mutations and appear to be mutually exclusive with germline RET mutation. The single most common somatic RAS mutation is HRASQ61R (c.182A>G), reported in 4.6% to 11% of all MTCs. Mutation-specific immunohistochemistry (IHC) initially developed to identify the NRASQ61R mutation in melanoma (clone SP174) has proven highly sensitive and specific...
January 2017: American Journal of Surgical Pathology
#24
JOURNAL ARTICLE
J Hadoux, O Féraud, F Griscelli, P Opolon, D Divers, E Gobbo, M Schlumberger, A Bennaceur-Griscelli, A G Turhan
Multiple Endocrine Neoplasia Type 2A (MEN2A) is a cancer-predisposing syndrome that affects patients with germline RET mutations. The clinical spectrum of the syndrome includes medullary thyroid carcinoma (MTC), pheochromocytoma, hyperparathyroidism and cutaneous lichen amyloidosis (CLA) and/or Hirschsprung disease in some variants. Currently, there is no satisfactory animal model recapitulating all the features of the disease especially at the level of stem cells. We generated induced pluripotent stem cells (iPSCs) from a patient with RET mutation at codon 634 who developed pheochromocytoma and MTC...
July 2016: Stem Cell Research
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REVIEW
Yulong Li, William F Simonds
Familial syndromes of hyperparathyroidism, including multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2A (MEN2A), and the hyperparathyroidism-jaw tumor (HPT-JT), comprise 2-5% of primary hyperparathyroidism cases. Familial syndromes of hyperparathyroidism are also associated with a range of endocrine and nonendocrine tumors, including potential malignancies. Complications of the associated neoplasms are the major causes of morbidities and mortalities in these familial syndromes, e...
June 2016: Endocrine-related Cancer
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JOURNAL ARTICLE
Sergei E Titov, Mikhail K Ivanov, Elena V Karpinskaya, Elena V Tsivlikova, Sergei P Shevchenko, Yulia A Veryaskina, Larisa G Akhmerova, Tatiana L Poloz, Olesya A Klimova, Lyudmila F Gulyaeva, Igor F Zhimulev, Nikolay N Kolesnikov
BACKGROUND: The postoperative typing of thyroid lesions, which is instrumental in adequate patient treatment, is currently based on histologic examination. However, it depends on pathologist's qualification and can be difficult in some cases. Numerous studies have shown that molecular markers such as microRNAs and somatic mutations may be useful to assist in these cases, but no consensus exists on the set of markers that is optimal for that purpose. The aim of the study was to discriminate between different thyroid neoplasms by RT-PCR, using a limited set of microRNAs selected from literature...
March 9, 2016: BMC Cancer
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JOURNAL ARTICLE
Ruta Sahasrabudhe, Jacob Stultz, John Williamson, Paul Lott, Ana Estrada, Mabel Bohorquez, Claire Palles, Guadalupe Polanco-Echeverry, Emma Jaeger, Lynn Martin, Maria Magdalena Echeverry, Ian Tomlinson, Luis G Carvajal-Carmona
CONTEXT: A recent study reported the non-synonymous G534E (rs7080536, allele A) variant in the HABP2 gene as causal in familial non-medullary thyroid cancer (NMTC). OBJECTIVE: The objective of this study was to evaluate the causality of HABP2 G534E in the TCUKIN study, a multi-center population based study of NMTC cases from the British Isles. DESIGN AND SETTING: A case-control analysis of rs7080536 genotypes was performed using 2,105 TCUKIN cases and 5,172 UK controls...
March 1, 2016: Journal of Clinical Endocrinology and Metabolism
#28
JOURNAL ARTICLE
Vincenzo Quagliariello, Emilia Armenia, Caterina Aurilio, Francesco Rosso, Ottavia Clemente, Gabriele de Sena, Manlio Barbarisi, Alfonso Barbarisi
The aim of this paper is based on the use of a hyaluronic acid hydrogel of Quercetin tested alone and in combination to an inhibitor of Aurora Kinase type A and B (SNS-314) on human medullary and papillary thyroid cancer cells. Biological investigations were focused on the cellular uptake of the hydrogel, cell viability, antioxidant, and cytokines secretion studies. Quercetin delivered from hydrogel show a time and CD44 dependent interaction with both cell lines with significant anti-inflammatory effects. Combination of Quercetin and SNS-314 leads to a synergistic cytotoxic effect on medullary TT and papillary BCPAP cell lines with a significant reduction of the IC50 value...
August 2016: Journal of Cellular Physiology
#29
JOURNAL ARTICLE
Claudia Scollo, Marco Russo, Laura De Gregorio, Rosa Terranova, Erika Mangione, Carlotta Castoro, Sebastiano Squatrito, Gabriella Pellegriti
Pheochromocytoma (Pheo) is a chromaffin tumor arising from the adrenal medulla. The recent discovery of new germline mutations in RET, SDHA, SDHB, SDHC, SDHD, VHL, NF1, TMEM127, MAX genes, increased the rate of genetic disease from 10% to 28% in patients with apparently sporadic tumor. RET germline mutations cause multiple endocrine neoplasia type 2 syndrome (MEN 2A) characterized by complete penetrance of medullary thyroid cancer (MTC), and lower prevalence of Pheo and hyperparathyroidism. We describe the genetic etiology of an apparently sporadic case of monolateral Pheo in a 42-year-old male patient...
2016: Endocrine Journal
#30
REVIEW
D Schmid, C Ricci, G Behrens, M F Leitzmann
Thyroid cancer incidence has increased rapidly over time, as has obesity prevalence. A link between the two appears plausible, but the relation of adiposity to thyroid cancer remains incompletely understood. We performed a meta-analysis of adiposity measures and thyroid cancer using studies identified through October 2014. Twenty-one articles yielded data on 12,199 thyroid cancer cases. We found a statistically significant 25% greater risk of thyroid cancer in overweight individuals and a 55% greater thyroid cancer risk in obese individuals as compared with their normal-weight peers...
December 2015: Obesity Reviews
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JOURNAL ARTICLE
Farzan Abdolahi, Mohammad Hossein Dabbaghmanesh, Mohammad Reza Haghshenas, Abbas Ghaderi, Nasrollah Erfani
Thyroid cancer is the most common malignancy of the endocrine system, and genetic factors have been shown to be associated with its risk. Interleukin-18 (IL-18) is a pleiotropic pro-inflammatory cytokine that induces IFN-γ production and is involved in T helper type 1 development. To determine the role of IL-18 gene in thyroid cancer susceptibility, we conducted a case-control study, and genotyped five single nucleotide polymorphisms (SNPs) in IL-18 gene (-656 G/T (rs1946519), -607 C/A (rs1946518), and -137 G/C (rs187238) in the promoter region and +113 T/G (rs360718) and +127 C/T (rs360717) in 5'-untranslated region) in 105 patients with thyroid cancer and 148 healthy controls from Iranian population...
December 2015: Endocrine
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JOURNAL ARTICLE
R Michael Tuttle, Robert I Haddad, Douglas W Ball, David Byrd, Paxton Dickson, Quan-Yang Duh, Hormoz Ehya, Megan Haymart, Carl Hoh, Jason P Hunt, Andrei Iagaru, Fouad Kandeel, Peter Kopp, Dominick M Lamonica, William M Lydiatt, Judith McCaffrey, Jeffrey F Moley, Lee Parks, Christopher D Raeburn, John A Ridge, Matthew D Ringel, Randall P Scheri, Jatin P Shah, Steven I Sherman, Cord Sturgeon, Steven G Waguespack, Thomas N Wang, Lori J Wirth, Karin G Hoffmann, Miranda Hughes
These NCCN Guidelines Insights focus on some of the major updates to the 2014 NCCN Guidelines for Thyroid Carcinoma. Kinase inhibitor therapy may be used to treat thyroid carcinoma that is symptomatic and/or progressive and not amenable to treatment with radioactive iodine. Sorafenib may be considered for select patients with metastatic differentiated thyroid carcinoma, whereas vandetanib or cabozantinib may be recommended for select patients with metastatic medullary thyroid carcinoma. Other kinase inhibitors may be considered for select patients with either type of thyroid carcinoma...
December 2014: Journal of the National Comprehensive Cancer Network: JNCCN
#33
JOURNAL ARTICLE
F Raue, T Wilhelm
CLINICAL ISSUE: Multiple endocrine neoplasia (MEN) types 1 and 2 are hereditary cancer syndromes. They are characterized by the occurrence of many benign and malignant tumor types. STANDARD TREATMENT: Carriers of a MEN1 or RET gene mutation can be identified before manifestation of the disease. Family screening allows the early diagnosis and therapy of gene carriers. TREATMENT INNOVATIONS: Early thyroidectomy in young patients with MEN2 results in a high cure rate of medullary thyroid carcinoma (MTC)...
October 2014: Der Radiologe
#34
JOURNAL ARTICLE
Uiju Cho, Woo Jin Oh, Ja Seong Bae, Sohee Lee, Young Sub Lee, Gyeong Sin Park, Youn Soo Lee, Chan Kwon Jung
The most common BRAF mutation in thyroid cancer is c.1799T>A (p.Val600Glu), and other BRAF mutations are rarely reported. We investigated the clinicopathological features of thyroid cancer with rare BRAF mutations. A total of 2,763 patients with thyroid cancer underwent molecular testing by direct DNA sequencing for mutations in BRAF exon 15. Among them, 2,110 (76.4%) had BRAF mutations. The c.1799T>A mutation was found in 2,093 (76.9%) of 2,722 papillary carcinomas and in one of 7 medullary carcinomas...
August 2014: Journal of Korean Medical Science
#35
JOURNAL ARTICLE
S Roosenburg, P Laverman, L Joosten, M S Cooper, P K Kolenc-Peitl, J M Foster, C Hudson, J Leyton, J Burnet, W J G Oyen, P J Blower, S J Mather, O C Boerman, J K Sosabowski
Cholecystokinin-2 (CCK-2) receptors, overexpressed in cancer types such as small cell lung cancers (SCLC) and medullary thyroid carcinomas (MTC), may serve as targets for peptide receptor radionuclide imaging. A variety of CCK and gastrin analogues has been developed, but a major drawback is metabolic instability or high kidney uptake. The minigastrin analogue PP-F11 has previously been shown to be a promising peptide for imaging of CCK-2 receptor positive tumors and was therefore further evaluated. The peptide was conjugated with one of the macrocyclic chelators DOTA, NOTA, or NODAGA...
November 3, 2014: Molecular Pharmaceutics
#36
JOURNAL ARTICLE
R Elisei, M Alevizaki, B Conte-Devolx, K Frank-Raue, V Leite, G R Williams
Twenty-five percent of medullary thyroid cancers (MTC) are familial and inherited as an autosomal dominant trait. Three different phenotypes can be distinguished: multiple endocrine neoplasia (MEN) types 2A and 2B, in which the MTC is associated with other endocrine neoplasias, and familial MTC (FMTC), which occurs in isolation. The discovery that germline RET oncogene activating mutations are associated with 95-98% of MEN 2/FMTC syndromes and the availability of genotyping to identify mutations in affected patients and their relatives has revolutionized the diagnostic and therapeutic strategies available for the management of these patients...
January 2013: European Thyroid Journal
#37
JOURNAL ARTICLE
Frederic Castinetti, Xiao-Ping Qi, Martin K Walz, Ana Luiza Maia, Gabriela Sansó, Mariola Peczkowska, Kornelia Hasse-Lazar, Thera P Links, Sarka Dvorakova, Rodrigo A Toledo, Caterina Mian, Maria Joao Bugalho, Nelson Wohllk, Oleg Kollyukh, Letizia Canu, Paola Loli, Simona R Bergmann, Josefina Biarnes Costa, Ozer Makay, Attila Patocs, Marija Pfeifer, Nalini S Shah, Thomas Cuny, Michael Brauckhoff, Birke Bausch, Ernst von Dobschuetz, Claudio Letizia, Marcin Barczynski, Maria K Alevizaki, Malgorzata Czetwertynska, M Umit Ugurlu, Gerlof Valk, John T M Plukker, Paola Sartorato, Debora R Siqueira, Marta Barontini, Malgorzata Szperl, Barbara Jarzab, Hans H G Verbeek, Tomas Zelinka, Petr Vlcek, Sergio P A Toledo, Flavia L Coutinho, Massimo Mannelli, Monica Recasens, Lea Demarquet, Luigi Petramala, Svetlana Yaremchuk, Dmitry Zabolotnyi, Francesca Schiavi, Giuseppe Opocher, Karoly Racz, Andrzej Januszewicz, Georges Weryha, Jean-Francois Henry, Thierry Brue, Bernard Conte-Devolx, Charis Eng, Hartmut P H Neumann
BACKGROUND: The prevention of medullary thyroid cancer in patients with multiple endocrine neoplasia type 2 syndrome has demonstrated the ability of molecular diagnosis and prophylactic surgery to improve patient outcomes. However, the other major neoplasia associated with multiple endocrine neoplasia type 2, phaeochromocytoma, is not as well characterised in terms of occurrence and treatment outcomes. In this study, we aimed to systematically characterise the outcomes of management of phaeochromocytoma associated with multiple endocrine neoplasia type 2...
May 2014: Lancet Oncology
#38
JOURNAL ARTICLE
Goran Cvijovic, Dragan Micic, Aleksandra Kendereski, Svetlana Zoric, Mirjana Sumarac-Dumanovic, Svetislav Tatic, Aleksandar Trivic, Danica Pejkovic-Stamenkovic, Danka Jeremic
OBJECTIVE: Serum calcitonin (CT) is a sensitive but not specific marker for medullary thyroid carcinoma (MTC). There are a large number of conditions that may elevate CT levels. CASE REPORT: Herein we present the case of a 47-year old woman with Hashimoto thyroiditis, goiter, cervical lymphadenopathy and high CT and CEA levels. After surgical extirpation of the lymph node neuroendocrine cancer metastasis was suspected. Computed tomography of the chest showed a tumor mass on the right lung...
October 2013: Hormones: International Journal of Endocrinology and Metabolism
#39
JOURNAL ARTICLE
Sonali Thosani, Montserrat Ayala-Ramirez, Lynn Palmer, Mimi I Hu, Thereasa Rich, Robert F Gagel, Gilbert Cote, Steven G Waguespack, Mouhammed Amir Habra, Camilo Jimenez
CONTEXT: Pheochromocytoma (PHEO) occurs in 50% of patients with multiple endocrine neoplasia type 2 (MEN2). It is unknown if the presence of PHEO is associated with more aggressive medullary thyroid cancer (MTC). OBJECTIVE: To present our experience with MEN2 PHEO and evaluate whether PHEO impacts MTC overall survival in patients with RET codon 634 mutations. DESIGN: We performed a retrospective chart review of MEN2 patients at MD Anderson Cancer Center from 1960 through 2012...
November 2013: Journal of Clinical Endocrinology and Metabolism
#40
MULTICENTER STUDY
Sarah E Kerr, Catherine A Schnabel, Peggy S Sullivan, Yi Zhang, Vivian J Huang, Mark G Erlander, Elena F Brachtel, Sarah M Dry
A diagnosis of neuroendocrine carcinoma is often morphologically straight-forward; however, the tumor site of origin may remain elusive in a metastatic presentation. Neuroendocrine tumor subtyping has important implications for staging and patient management. In this study, the novel use and performance of a 92-gene molecular cancer classifier for determination of the site of tumor origin are described in a series of 75 neuroendocrine tumors (44 metastatic, 31 primary; gastrointestinal (n=12), pulmonary (n=22), Merkel cell (n=10), pancreatic (n=10), pheochromocytoma (n=10), and medullary thyroid carcinoma (n=11))...
January 2014: Modern Pathology
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