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Anaplastic Thyroid Carcinoma (anaplastic + thyroid_carcinoma)
Selected AbstractsAirway Management in Anaplastic Thyroid Carcinoma,THE LARYNGOSCOPE, Issue 7 2008Ashok R. Shaha MD Abstract Objectives/Hypothesis: In patients who present with advanced anaplastic thyroid cancer, airway management is difficult because of bilateral vocal cord paralysis or tracheal invasion by the tumor. Airway management can be extremely complex in these patients. Study Design: This is the author's 25 year experience with 30 patients who presented with anaplastic thyroid cancer and acute airway problems. Methods: The patients' airway issues developed soon after presentation or a few months after treatment. Ten patients presented with initial symptoms of acute airway distress. All of these patients were treated with tracheostomy or cricothyrotomy. Results: The 10 patients who presented with initial symptoms of acute airway distress died within 4 months. Eight of the remaining 20 patients developed bilateral vocal cord paralysis. Airway management for these patients depended on the extent of distant disease and the family's understanding of the advanced nature of the disease and the palliative efforts. The remaining patients had a palliative and supportive approach. Conclusions: Airway management was the most critical issue in patients who presented with anaplastic thyroid cancer and initial airway distress. Cricothyrotomy was helpful in avoiding acute airway catastrophe. It is important to distinguish between poorly differentiated and anaplastic thyroid cancer and lymphoma for appropriate airway management. [source] ITCH is a putative target for a novel 20q11.22 amplification detected in anaplastic thyroid carcinoma cells by array-based comparative genomic hybridizationCANCER SCIENCE, Issue 10 2008Takaya Ishihara Anaplastic thyroid carcinoma (ATC) is one of the most virulent of all human malignancies, with a mean survival time among patients of less than 1 year after diagnosis. To date, however, cytogenetic information on this disease has been very limited. During the course of a program to screen a panel of ATC cell lines for genomic copy-number aberrations using array-based comparative genomic hybridization, we identified a high-level amplification of the ITCH gene, which is mapped to 20q11.22 and belongs to the homologous to the E6-associated protein carboxylterminus ubiquitin ligase family. The expression of ITCH was increased in 4 of 14 ATC cell lines (28.6%), including 8305C in which there was a copy-number amplification of this gene, and six of seven primary cases (85.7%). Among the primary thyroid tumors, a considerable number of ITCH high expressers was found in ATC (40/45, 88.9%), papillary thyroid carcinoma (25/25, 100%), and papillary microcarcinoma (25/25, 100%). Furthermore, knockdown of ITCH by specific small interfering RNA significantly inhibited the growth of ITCH-overexpressing cells, whereas ectopic overexpression of ITCH promoted growth of ATC cell lines with relatively weak expression. These observations indicate ITCH to be the most likely target for 20q11.22 amplification and to play a crucial role in the progression of thyroid carcinoma. (Cancer Sci 2008; 99: 1940,1949) [source] Peroxisome Proliferator-activated Receptor Gamma Activation Induces Cell Cycle Arrest via the p53-independent Pathway in Human Anaplastic Thyroid Cancer CellsCANCER SCIENCE, Issue 12 2002Sung Hwa Chung Anaplastic thyroid carcinoma is one of the most aggressive human malignancies. Outcomes of intensive multimodal therapy have been far from satisfactory. Furthermore, p53 gene dysfunction, often found in this type of cancer, is known to impair the efficacy of the therapeutic agents. Specific ligands for peroxisome proliferator activated receptor gamma (PPAR-,) induce growth suppression in some tumor cells. In this study, we investigated the role of PPAR-, in anaplastic thyroid cancer cell lines (OCUT-1, ACT-1). PPAR-, was expressed and functional in both cell lines. Activation of PPAR-, with its specific ligands, troglitazone and 15-deoxy-,12, 14 -prostaglandin J2, inhibited cell growth in a dose-dependent manner through inducing G1 cell cycle arrest. P53 protein expression differed in OCUT-1 and in ACT-1, though the levels stayed constant irrespective of ligand exposure in both cell lines. In contrast, p21 and p27 proteins were induced in a dose-dependent manner in both situations. This study showed that PPAR-, ligands were able to induce growth suppression in anaplastic thyroid cancer cells via a p53-independent, but p21- and p27-dependent cytostatic pathway. These tumor-suppressive effects of PPAR-, may provide a novel approach to the treatment of anaplastic thyroid cancer. [source] Growth inhibition of orthotopic anaplastic thyroid carcinoma xenografts in nude mice by PTK787/ZK222584 and CPT-11HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 5 2006Seungwon Kim MD Abstract Background. A preclinical evaluation of CPT-1 (Camptosar, irinotecan) and PTK787/ZK222584, a vascular endothelial growth factor receptor (VEGFR-2) tyrosine kinase inhibitor, as therapeutic agents against anaplastic thyroid carcinoma (ATC) was performed in vitro and in an orthotopic model of ATC in nude mice. Methods. The cytotoxic and cytostatic effects of CPT-11 on ATC cell lines were evaluated. The antitumor effects of CPT-11 in combination with PTK787/ZK222584 on orthotopic ATC xenografts in nude mice were also studied. Results. CPT-11 demonstrated significant antiproliferative effects on ATC cell lines. In vivo, PTK787/ZK222584, CPT-11, and the two agents together produced 61%, 82%, and 89% decrease in tumor growth, respectively. The differences in tumor volume between CPT-11 and CPT-11 + PTK787/ZK222584 groups were not statistically significant. PTK787/ZK222584 inhibited the phosphorylation of VEGFR-2 on tumor endothelium and decrease the tumor microvessel density. Conclusions. The camptothecin class of chemotherapeutic agents and antiangiogenic agents such as PTK787/ZK222584 warrant further study as novel therapeutic agents against ATC. © 2005 Wiley Periodicals, Inc. Head Neck27: 389,399, 2006 [source] Prognostic factors in patients with Hürthle cell neoplasms of the thyroidCANCER, Issue 5 2003Luis Lopez-Penabad M.D. Abstract BACKGROUND Hürthle cell neoplasms, often considered a variant of follicular thyroid neoplasms, represent 3% of thyroid carcinomas. Only a handful of publications have focused on the biologic behavior, prognostic factors, and treatment outcomes of Hürthle cell carcinoma. The objective of the current study was to identify the clinical and pathologic features of Hürthle cell carcinomas that predict disease progression or death. METHODS The authors reviewed medical records of patients who were treated for Hürthle cell carcinoma (HCC) and Hürthle cell adenoma (HCA) at The University of Texas M. D. Anderson Cancer Center from March 1944 to February 1995, including follow-up information. The pathologic diagnosis was confirmed by one of the authors. RESULTS The authors identified 127 patients with Hürthle cell neoplasms, 89 patients with HCC and 38 patients with HCA. Seven patients with HCC had foci of anaplastic thyroid carcinoma. Survival for this subgroup was worse compared with the overall group and was analyzed separately. The HCC group was significantly older (age 51.8 years vs. age 43.1. years) and had larger tumors (4.3 cm vs. 2.9 cm) compared with the HCA group. No differences were seen in gender or previous radiation exposure. Forty percent of patients in the HCC group died of thyroid carcinoma, whereas no patients in the HCA group died of the disease. There has been no improvement in all-cause and disease specific mortality in the past 5 decades for patients with these neoplasms. Conventional staging systems predicted mortality with minor differences. Of the patients with known metastasis, 38% showed radioiodine uptake. Univariate analysis identified older age, higher disease stage, tumor size, extraglandular invasion, multifocality, lymph node disease, distant metastasis, extensive surgery, external beam radiation therapy, and chemotherapy as factors that were associated with decreased survival. Tumor encapsulation was associated with improved survival. Although radioactive iodine treatment had no overall effect on survival, subgroup analysis showed that patients who received radioactive iodine for adjuvant ablation therapy had better outcomes compared either with patients who did not receive radioactive iodine or with patients who received radioactive iodine as treatment for residual disease. Multivariate analysis indicated that older age and larger tumor size predicted worse survival through an association with worse behaving tumors (multifocal, less encapsulated, and with extraglandular invasion). The decreased survival in patients with lymph node metastases may be explained by its association with distant metastases. The association of extensive surgery, external beam radiation therapy, and chemotherapy with worse survival also disappeared once those factors were analyzed together with other prognostic factors, such as distant metastases. CONCLUSIONS Several clinical and pathologic prognostic factors were identified in patients with HCC and HCA. Older age and larger tumor size predicted reduced survival. Radioactive iodine therapy may confer a survival benefit when it is used for adjuvant ablation therapy, but not when residual disease is present. The authors could not demonstrate a survival benefit for the use of extensive surgery, external beam radiation therapy, or chemotherapy. Cancer 2003;97:1186,94. © 2003 American Cancer Society. DOI 10.1002/cncr.11176 [source] Aberrant BRAF splicing as an alternative mechanism for oncogenic B-Raf activation in thyroid carcinoma,THE JOURNAL OF PATHOLOGY, Issue 5 2009Essa Y Baitei Abstract Activating BRAF mutations have recently been reported in 28,83% of papillary thyroid carcinomas (PTCs). However, it is not known whether aberrant BRAF splicing occurs in thyroid carcinoma. To investigate aberrant BRAF splicing and its association with BRAF mutation in thyroid tumours, we studied aberrant BRAF splicing and BRAF mutation from 68 thyroid tumours. BRAFV600E mutation was detected in 20 of 43 PTCs and all three anaplastic thyroid carcinomas (ATCs). There is a higher frequency of BRAF mutation in PTC patients with stage III and IV tumours compared with stage I and II. Novel BRAF splicing variants were detected in 12 PTCs, three follicular variants of PTC (FVPTCs), and one ATC, as well as in two thyroid carcinoma cell lines, ARO and NPA. These variants did not have the N-terminal auto-inhibitory domain of wild-type B-Raf, resulting in an in-frame truncated protein that contained only the C-terminal kinase domain and caused constitutive activation of B-Raf. These variants were significantly associated with advanced disease stage and BRAFV600E mutation (p < 0.001, Fisher exact test). Furthermore, expression of these variants in NIH3T3 and CHO cells could activate the MAP kinase signalling pathway, transform them in vitro, and induce tumours in nude mice. These data suggest that BRAF splicing variants may function as an alternative mechanism for oncogenic B-Raf activation. Combination of the BRAFV600E mutation and its splicing variants may contribute towards disease progression to poorly differentiated thyroid carcinoma. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Aneuploidy and RAS mutations are mutually exclusive events in the development of well-differentiated thyroid follicular tumoursCLINICAL ENDOCRINOLOGY, Issue 5 2007Ana Banito Summary Objective, Follicular thyroid tumours present several genetic alterations such as aneuploidy, RAS mutations and PAX8/PPAR,rearrangements. The molecular basis of aneuploidy remains undefined in the majority of human cancers. It has been proposed that mutations in RAS oncogenes could be related to chromosomal instability, although this issue remains controversial. The aim of our study was to investigate the correlation between aneuploidy, RAS mutations and PAX8/PPAR, gene rearrangement in thyroid follicular tumours. Design, Ploidy status was determined by flow cytometry in 111 thyroid lesions (42 follicular thyroid adenomas, 27 follicular thyroid carcinomas, 19 follicular variants of papillary thyroid carcinoma, 20 poorly differentiated thyroid carcinomas and 3 anaplastic thyroid carcinomas). RAS mutations and PAX8/PPAR, fusion gene were investigated in 101 and 87 of these samples, respectively. Results, Altogether, 12 of 50 (24%) diploid tumours presented RAS mutation which contrasts with 3 of 51 (5·9%; P = 0·0124) RAS mutations in the group of aneuploid tumours. The aneuploid tumours harbouring RAS mutations were two poorly differentiated carcinomas and one follicular variant of papillary thyroid carcinoma with poorly differentiated areas. None of the tumours with RAS mutations expressed the PAX8/PPAR, fusion gene. Three of five (60%) follicular thyroid adenomas and 1 of 7 (14%) follicular thyroid carcinomas, with the PAX8/PPAR, fusion gene, were aneuploid. Conclusions, Our data suggest that aneuploidy and RAS mutations are mutually exclusive events in the development of well-differentiated thyroid follicular tumours. [source] | ||||||||||