Derangement of p53 and MDM2 is involved in transformation of differentiated into anaplastic thyroid cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5556-5556 ◽  
Author(s):  
S. M. Wiseman ◽  
H. Masoudi ◽  
P. Niblock ◽  
D. Turbin ◽  
A. Rajput ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Tumor Progression ◽  
Anaplastic Thyroid Cancer ◽  
Differentiated Thyroid Carcinoma ◽  
Thyroid Tumor ◽  
Thyroid Tumors ◽  
P53 Overexpression ◽  
Anaplastic Transformation ◽  
Mdm2 Overexpression

5556 Background: Anaplastic thyroid cancer arises as a consequence of tumor progression, or transformation, from pre-existing differentiated thyroid cancer. Mutation of the p53 tumor-suppressor gene represents a common event in thyroid tumor progression. MDM2 encodes a protein that complexes with p53, downregulates its function, and leads to its degradation via a ubiquitin-proteasome pathway. The objective of this study was to evaluate the change in p53 and MDM2 expression in the transformation of differentiated to anaplastic thyroid carcinoma. Methods: Of 94 cases of anaplastic thyroid cancer diagnosed and treated in British Columbia Canada over a 20 year period (1984–2004) 32 cases (34%) had adequate tissue available for evaluation and 12 of these cases had associated foci of differentiated thyroid carcinoma. A tissue microarray was constructed from these 12 anaplastic thyroid tumors and their associated differentiated foci. Immunohistochemistry was utilized to evaluate expression of p53 and MDM2 by these tumors. Results: There was decreased expression of p53 and MDM2 by the anaplastic tumors when compared to the differentiated thyroid tumors from which they evolved. The expression of p53 and MDM2 was 17% and 8%, respectively, by the differentiated thyroid carcinoma, and 83% and 25%, respectively, by the anaplastic tumors. Evaluating the anaplastic cancers and the differentiated foci from which they evolved, p53 overexpression developed in 8 (67%) of tumors and MDM2 overexpression developed in 3 (25%) of tumors. All the anaplastic tumors that developed MDM2 overexpression also concurrently developed p53 overexpression. Conclusions: This report is the first to demonstrate derangement of p53, and its regulator, MDM2, is involved in the transformation of a subset of differentiated into anaplastic thyroid tumors. Isolated MDM2 overexpression does not appear to play an important role in anaplastic transformation of thyroid cancer. No significant financial relationships to disclose.

scholarly journals Anaplastic thyroid carcinoma

2003 ◽  
Vol 50 (3) ◽  
pp. 131-134
Author(s):  
Vladan Zivaljevic ◽  
Aleksandar Diklic ◽  
Ivan Paunovic ◽  
Ksenija Krgovic ◽  
Rastko Zivic ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Surgical Treatment ◽  
Thyroid Carcinoma ◽  
Cancer Patients ◽  
Anaplastic Thyroid Cancer ◽  
Anaplastic Thyroid Carcinoma ◽  
Endocrine Surgery ◽  
Papillary Thyroid ◽  
Anaplastic Transformation ◽  
Tumor Reduction

The aim of the present paper was to study some characteristics and posibility of surgery of anaplastic thyroid cancer. During five years period in Center for endocrine surgery, we found anaplastic thyroid cancer in 65 patienst (44 female and 21 male), median age 63 years (from 37 to 88 years). Surgical treatment was peerformed in one half (32) anaplastic thyroid cancer patients, at majority of them operative biopsy or tumor reduction only. Radical syrgery was performed in about 10% patients. Posibility of surgery in anaplastic thyroid cancer are very limited. In one third patients there were longstanding goter or thyroid nodul or histological verified dediferentiation of papillary thyroid cancer. This patienst should be operated formerly, before anaplastic transformation.

scholarly journals Anaplastic thyroid carcinoma diagnosed after treatment of lenvatinib for papillary thyroid carcinoma

2019 ◽  
Vol 2019 ◽  
Author(s):  
Haruhiko Yamazaki ◽  
Hiroyuki Iwasaki ◽  
Nobuyasu Suganuma ◽  
Soji Toda ◽  
Katsuhiko Masudo ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Core Needle Biopsy ◽  
Needle Biopsy ◽  
Differentiated Thyroid Carcinoma ◽  
Target Lesion ◽  
Thyroid Tumor ◽  
Papillary Thyroid ◽  
Core Needle ◽  
Anaplastic Transformation

Summary Anaplastic transformation of a primary thyroid tumor whose process can be followed is rare. The objective this study is to report a case of anaplastic transformation of locally advanced papillary thyroid carcinoma after treatment with lenvatinib. A 74-year-old woman consulted a local physician because of cough and bloody sputum. Thyroid cancer with tracheal invasion was suspected on computed tomography (CT) imaging, and she visited our hospital for treatment. We suspected anaplastic thyroid cancer (ATC) and core needle biopsy was performed. Histologic sections of the core needle biopsy showed that the tumor formed a papillary structure, and we diagnosed papillary thyroid carcinoma. Surgery would have been difficult, and we initiated lenvatinib at a low dose of 8 mg/day. CT on day 40 of lenvatinib treatment revealed that the thyroid tumor had shrunk remarkably. CT on day 111 revealed that tumor regrowth and tracheal invasion had been exacerbated. Core needle biopsy was performed, and histologic sections of the core needle biopsy that was performed after regrowth of the tumor showed that individual cancer cells had large, irregular nuclei, and necrosis was also observed. The immunohistochemical findings were negative for thyroglobulin, and only a few cells were positive for thyroid transcription factor 1, and we diagnosed ATC. Anaplastic transformation of the target lesion may be one of the causes of lenvatinib treatment failure in differentiated thyroid carcinoma. Learning points: Anaplastic transformation of a primary thyroid tumor whose process can be followed is rare. The resistance mechanism of lenvatinib in treatment for differentiated thyroid carcinoma has not been clarified. Anaplastic transformation of the target lesion may be one of the causes of lenvatinib treatment failure in differentiated thyroid carcinoma.

scholarly journals Ptimary thyroid lymphomas and other rare thyroid tumors

2003 ◽  
Vol 50 (3) ◽  
pp. 141-146 ◽  
Author(s):  
Aleksandar Diklic ◽  
Vladan Zivaljevic ◽  
Ivan Paunovic ◽  
Ksenija Krgovic ◽  
Rastko Zivic ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Residual Tumor ◽  
Hashimoto Thyroiditis ◽  
Local Relapse ◽  
Thyroid Tumor ◽  
Recurrent Nerve ◽  
Thyroid Tumors ◽  
Treatment Frequency ◽  
Recurrent Nerve Palsy

Primary thyroid lymphomas are rare. Surgery is seldom indicated. The aim of the study is to find out the main characteristics of primary thyroid lymphomas in our patients, indications for surgery and the possibility of treatment, frequency and characteristics of rare thyroid tumors. Method: retrospective study of 1044 patient operated for malignant thyroid tumor. Results: From 1995 to may 2003, we operated upon 15 patients with primary thyroid lymphomas, 2 men and 13 women mean age of 50.12 years (from 22 to 74 years), also one patient of age 69 with insular thyroid cancer. Reason for surgery was thyroid tumor in all, compressive disturbances in 9, among them 4 with asphyxia. Radical total thyroidectomy was performed in 4 (26.7%), whole in others some residual tumor tissue was could not be removed in spite of thyroidectomy in 3, hemithyroidectomy in 2, tumor debulking in 5 and only open biopsy was performed in one patient. There was no operative mortality, no postoperative hypocalcaemia and no recurrent nerve palsy. Histological type of tumor was Non-Hodgkin lymphoma in 13 patients, Hodgkin disease in 2 female patients of age 22 and 24. Hashimoto thyroiditis was present in 3 patients. After surgery, 13 patients were treated with chemotherapy, one patient died one month after the operation and one patient refused chemotherapy. Follow-up data are available for 9 patients and the mean follow-up period was 20 months (1-48months). Three patients died after a month, 2 and 3 years after surgery. Six patients are without local relapse. In one patient who refused chemotherapy, a year after thyroid surgery, resection of large intestine was performed because of lymphoma of the colon. Conclusion: Malignant thyroid lymphomas are rare. They present with rapidly growing thyroid tumor, compression and asphyxia. Surgery is only temporarily effective and it is necessary to start with chemo-radiotherapy as soon as possible. Rare forms of thyroid cancer have to be histological recognized in order to choose the best way of treatment.

scholarly journals Brain Metastases From Differentiated Thyroid Carcinoma: Prevalence, Current Therapies, and Outcomes

2018 ◽  
Vol 3 (2) ◽  
pp. 359-371 ◽  
Author(s):  
Cristiane J Gomes-Lima ◽  
Di Wu ◽  
Sarika N Rao ◽  
Sree Punukollu ◽  
Rama Hritani ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Brain Metastases ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Differentiated Thyroid Carcinoma ◽  
Unusual Site ◽  
Current Therapies ◽  
The Brain

Abstract Background and Objective The brain is an unusual site for distant metastases of differentiated thyroid carcinoma (DTC). The aim of this study was to document the prevalence of brain metastases from DTC at our institutions and to analyze the current therapies and the outcomes of these patients. Methods We performed a retrospective chart review of patients with DTC and secondary neoplasia of the brain. Results From 2002 to 2016, 9514 cases of thyroid cancer were evaluated across our institutions and 24 patients met our inclusion criteria, corresponding to a prevalence of 0.3% of patients with DTC. Fourteen (58.3%) were female and 10 (41.7%) were male. Fifteen patients had papillary thyroid cancer (PTC) (62.5%). Brain metastases were diagnosed 0 to 37 years (mean ± SD, 10.6 ± 10.4 years) after the initial diagnosis of thyroid cancer. Patients undergoing surgery had a median survival time longer than those that did not undergo surgery (27.3 months vs 6.8 months; P = 0.15). Patients who underwent stereotactic radiosurgery (SRS) had a median survival time longer than those that did not receive SRS (52.5 months vs 6.7 months; P = 0.11). Twelve patients (50%) were treated with tyrosine kinase inhibitors (TKIs), and they had a better survival than those who have not used a TKI (median survival time, 27.2 months vs 4.7 months; P < 0.05). Conclusion The prevalence of brain metastases of DTC in our institutions was 0.3% over 15 years. The median survival time after diagnosis of brain metastases was 19 months. In our study population, the use of TKI improved the survival rates.

scholarly journals Thyroid Carcinoma with Pituitary Metastases: 2 Case Reports and Literature Review

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Weiying Lim ◽  
Dawn Shaoting Lim ◽  
Chiaw Ling Chng ◽  
Adoree Yiying Lim
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Radioiodine Therapy ◽  
Follicular Thyroid Carcinoma ◽  
Case Reports ◽  
Anaplastic Thyroid Cancer ◽  
Anaplastic Thyroid Carcinoma ◽  
Pituitary Metastases ◽  
History Of ◽  
Loss Of Appetite

We present 2 patients with pituitary metastases from thyroid carcinoma—the first from anaplastic thyroid carcinoma and the second from follicular thyroid carcinoma. The first patient, a 50-year-old lady, presented with 2-week history of hoarseness of voice, dysphagia, dyspnoea, and neck swelling. Imaging revealed metastatic thyroid cancer to lymph nodes and bone. Histology from surgery confirmed anaplastic thyroid cancer. She was found to have pituitary metastases postoperatively when she presented with nonvertiginous dizziness. She subsequently underwent radiotherapy and radioiodine treatment but passed away from complications. The second patient, a 65-year-old lady, presented with loss of appetite and weight with increased goitre size and dyspnoea. Surgery was performed in view of compressive symptoms and histology confirmed follicular thyroid carcinoma. Imaging revealed metastases to bone, lung, and pituitary. She also had panhypopituitarism with hyperprolactinemia and diabetes insipidus. She received radioiodine therapy but eventually passed away from complications.

scholarly journals Lenvatinib Administered via Nasogastric Tube in Poorly Differentiated Thyroid Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-4 ◽  
Author(s):  
Eleonora Molinaro ◽  
David Viola ◽  
Nicola Viola ◽  
Pierpaolo Falcetta ◽  
Francesca Orsolini ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Gastric Tube ◽  
Kinase Inhibitors ◽  
Locally Advanced ◽  
Differentiated Thyroid Carcinoma ◽  
Cervical Esophagus ◽  
Extrinsic Compression ◽  
Poorly Differentiated ◽  
Iodine 131

Background. The tyrosine kinase inhibitors (TKIs) are indicated for the treatment of locally advanced or metastatic progressive thyroid carcinoma (CDT), refractory to radioactive iodine. The following report describes the efficacy of lenvatinib administered through a nose-gastric tube (SNG) in a patient affected with a poorly differentiated thyroid carcinoma (PDTC) which determined a stenosis of the esophagus. Material and Methods. A patient was followed up for papillary thyroid carcinoma follicular variant (T3NxMx), subjected to total thyroidectomy and treated with iodine-131 radio metabolic therapy. Two years after surgery, following the onset of dysphonia and dysphagia, patient was submitted to a computed tomography (CT) scan of the neck that showed the presence of a lesion of 6 × 2.5 × 3.5 cm, which determined trachea deviation and cervical esophagus compression. The biopsy indicated the presence of PDTC, triggering tracheal lumen reduction and sub-stenosis of the cervical esophagus for an ab-extrinsic compression. A nose-gastric tube (SNG) was placed and lenvatinib was started at a dose of 20 mg/day, administered via this probe after opening the capsules and diluting the drug in 10 ml of saline solution. Results. One month later, CT showed a significant cervical lesion reduction. Bronchoscopy confirmed tracheal infiltration, but the residual caliber was improved from 50% to 75%. At the esophagogastroduodenoscopy (EGDS), the sub stenosis of the cervical esophagus was no longer appreciated; however, a double perforation of the esophagus was found, without fistula. Conclusion. Lenvatinib therapy is effective also when administered via SNG. Our result is of particular relevance in the management of thyroid cancer patients, especially in the presence of subjects unable to swallow. Further studies are needed to validate the administration of lenvatinib by SNG, in order to extend the indications to this alternative administration way, beside the oral one.

scholarly journals A Case of Thyroid Papillary Carcinoma: Remarkable Decrease in Multiple Lung Metastases within 40 Years after a Single Administration of Radioiodine without Thyroidectomy and with Later Anaplastic Transformation

2017 ◽  
Vol 10 (3) ◽  
pp. 928-937 ◽  
Author(s):  
Chio Okuyama ◽  
Mitsuhiro Kimura ◽  
Minori Oda ◽  
Naohiro Kodani ◽  
Norihiro Aibe ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Total Thyroidectomy ◽  
Pulmonary Metastases ◽  
Lung Metastases ◽  
Distant Metastases ◽  
Anaplastic Thyroid Cancer ◽  
Anaplastic Carcinoma ◽  
High Rate ◽  
Childhood And Adolescence ◽  
Anaplastic Transformation

Differentiated thyroid carcinoma is an uncommon malignancy of childhood and adolescence that is unique because it has an overall favorable prognosis despite its relatively high rate of nodal and distant metastases. Total thyroidectomy and positive 131I therapy are recommended for cases with pulmonary metastases. In contrast, anaplastic thyroid cancer is one of the most aggressive malignancies that have an unfavorable and miserable prognosis. We report a case with an impressively long history. The patient had multiple pulmonary metastases that had been diagnosed by 131I administration when he was 14 years old, about 45 years before he underwent thyroidectomy. He had been kept unaware of his disease by his family and received no treatment for most of his life. Pulmonary nodules were noted at several medical checkups and showed a remarkable decrease in size during the untreated 44-year period after the 131I administration. At age 58, his thyroid cancer was first detected and total thyroidectomy was performed, with subsequent radioiodine therapy for pulmonary metastases. Unfortunately, anaplastic carcinoma developed and he died of disseminated tumors later.

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