Over-representation of a germline RET sequence variant in patients with sporadic medullary thyroid carcinoma and somatic RET codon 918 mutation.
The aetiology of sporadic medullary thyroid carcinoma is unknown. About 50% harbour a somatic mutation at codon 918 of RET (M918T). To investigate whether other RET sequence variants may be associated with or predispose to the development of sporadic medullary thyroid carcinoma, we analysed genomic DNA from the germline and corresponding tumour from 50 patients to identify RET sequence variants. In one patient, tumour DNA showed a novel somatic 12 bp in-frame deletion in exon 15. More interestingly, we found that the rare polymorphism at codon 836 (c.2439C > T; S836S) occurred at a significantly higher frequency than that in control individuals without sporadic medullary thyroid carcinoma (Fisher's exact test, P = 0.03). Further, among the nine evaluable cases with germline c.2439C/T, eight also had the somatic M918T mutation in MTC DNA which was more frequent than in patients with the more common c.2439C/C (89% vs 40%, respectively; Fisher's exact test, P = 0.01). These findings suggest that the rare sequence variant at codon 836 may somehow play a role in the genesis of sporadic medullary thyroid carcinoma. (+info)
Medullary thyroid carcinoma with multiple hepatic metastases: treatment with transcatheter arterial embolization and percutaneous ethanol injection.
A 54-year-old man with medullary thyroid carcinoma in the thyroid gland was unable to undergo total thyroidectomy because the tumor had invaded the mediastinum. Radiation therapy and chemotherapy were given. Seven years later, intractable diarrhea and abdominal pain appeared, and computed tomography demonstrated hypervascular tumors in the thyroid gland and in the liver. The tumors were successfully treated with percutaneous ethanol injection to a lesion in the thyroid gland and transcatheter arterial embolization followed by percutaneous ethanol injection to tumors in the liver. Transcatheter arterial embolization and percutaneous ethanol injection may be valuable in treating medullary thyroid carcinoma. (+info)
Epithelial thyroid tumors in cows.
From 1964 to 1973, 370 tumors were collected from cows of unknown age. Ten (2.7%) of these were primary thyroid tumors. Three were malignant. The benign tumors were solitary encapsulated adenomas in the parenchyma with more or less defined trabeculae, tubular, and microfollicular pattern. One of the malignant tumors was a cystic papillary adenocarcinoma, and two were small cell carcinomas consisting of small, sometimes binuclear, pleomorphic cells. (+info)
Overexpression of fibroblast growth factor receptor 3 in a human thyroid carcinoma cell line results in overgrowth of the confluent cultures.
Recent reports indicate that a gain-of-function mutation in fibroblast growth factor receptor 3 (FGFR-3) inhibits cell growth in the cartilaginous growth plates. These results suggest that FGFR-3 may be the receptor transducing growth inhibitory signals. Using reverse transcription-PCR we examined seven papillary thyroid carcinomas to determine FGFR-3 expression. Six out of the seven papillary carcinomas expressed FGFR-3. To clarify the role of FGFR-3 in thyroid carcinoma, FGFR-3 was overexpressed in an established human papillary thyroid carcinoma cell line. High levels of FGFR-3 protein were identified in cells stably transfected with the vector containing FGFR-3 cDNA. The specific binding of 125I-FGF-2 of these cells was threefold higher than that of control cells. Growth rates of cells overexpressing FGFR-3 were similar to those of control cells. However, cells overexpressing FGFR-3 continued to grow beyond the density at which control cells stopped proliferating. These results suggest that FGFR-3 in thyroid carcinoma is not involved strongly in the cell proliferation mechanism but may contribute to the malignant extension of some of the carcinomas by modifying cell contact signaling. (+info)
Psychosocial impact of genetic testing in familial medullary-thyroid carcinoma: a multicentric pilot-evaluation.
BACKGROUND: Many crucial problems are associated with the diagnosis of inherited cancer susceptibility. One of the most important is related to the psychosocial consequences of the knowledge by the patients and their relatives of their own genetical status. Little data are available in the literature, mainly from studies including small numbers of selected and motivated patients. PATIENTS AND METHODS: From January till December 1997, we studied the psychometric and quality of life parameters of 77 subjects followed in two French specialized centers. These subjects had been treated for either sporadic or familial or were at risk for medullary thyroid carcinoma. All patients had previously attended genetic counselling with detection of germline Ret-mutations, were informed on their own genetic risk, had good short-term prognosis and performance status and did not receive recent cancer treatment. Each patient was invited to answer two questionnaires, the hospital anxiety and depression scale (HADS) and the subjective quality of life profile (SQLP). RESULTS: We report herein the descriptive results of this study (HADS and SQLP scores and distributions) and describe the individual clinical covariates that might explain the observed differences between subgroups of individuals. Although psychometric scores appeared similar in these subgroups, quality of life scores were lower in Ret-mutation carriers. Genetically-predisposed patients were less satisfied and expressed more expectations for favourable change in their quality of life. CONCLUSION: This finding suggests a high level of frustration and latent unsatisfaction related either to the management of the genetic information given by the clinicians and its psychosocial consequences or simply to the knowledge of the genetic risk of cancer. Further studies on the individual consequences of genetic testing, information delivery and when necessary psychotherapeutic interventions, are needed to insure the quality of presymptomatic genetic testing in this field of oncology. (+info)
A new rapid technique for the fixation of thyroid gland surgical specimens.
One of the main diagnostic problems in thyroid pathology is to distinguish between follicular adenoma and follicular carcinoma. Thorough sampling of the nodule's capsule is recommended in order to identify capsular invasion. However, during the hardening of the tissue, by the usual fixatives the capsule shrinks and rolls downwards and sometimes the capsule separates from the remaining tissue. The present work evaluates the use of "Lymph Node Revealing Solution" (LNRS) for the rapid fixation (2h) of different thyroid lesions as compared to that of formalin. Fifty-one unselected consecutive cases of thyroid nodules, which included various benign and malignant lesions, were examined. Each specimen was cut in two equal parts; one was fixed in LNRS, the other in formalin. Fixation in LNRS for 2 hours gave adequate results in sectioning and staining of the tissue, and excellent immunostains. Its advantage over formalin is the conservation of the natural relationship between the capsule and the rest of the tissue, on the same plane, as well as the short time required for the final diagnosis. (+info)
Overexpression of c-Ras in hyperplasia and adenomas of the feline thyroid gland: an immunohistochemical analysis of 34 cases.
Formalin-fixed, paraffin-embedded thyroid glands from 18 cats diagnosed with hyperthyroidism were evaluated immunohistochemically for overexpression of the products of oncogenes c-ras and bcl2 and the tumor suppressor gene p53. Fourteen thyroid glands from euthyroid cats without histologically detectable thyroid lesions were examined similarly as controls. Results from these investigations showed that all cases of nodular follicular hyperplasia/adenomas stained positively for overexpression of c-Ras protein using a mouse monoclonal anti-human pan-Ras antibody. The most intensely positively staining regions were in luminal cells surrounding abortive follicles. Subjacent thyroid and parathyroid glands from euthyroid cats did not stain immunohistochemically for pan-Ras. There was no detectable staining for either Bc12 or p53 in any of the cats. These results indicated that overexpression of c-ras was highly associated with areas of nodular follicular hyperplasia/adenomas of feline thyroid glands, and mutations in this oncogene may play a role in the etiopathogenesis of hyperthyroidism in cats. (+info)
Human thyroid cancer cells as a source of iso-genic, iso-phenotypic cell lines with or without functional p53.
Differentiated thyroid carcinomas (in contrast to the rarer anaplastic form) are unusual among human cancers in displaying a remarkably low frequency of p53 mutation and appear to retain wild-type (wt) p53 function as assessed by the response of derived cell lines to DNA damage. Using one such cell line, K1, we have tested the effect of experimental abrogation of p53 function by generating matched sub-clones stably expressing either a neo control gene, a dominant-negative mutant p53 (143ala) or human papilloma virus protein HPV16 E6. Loss of p53 function in the latter two groups was confirmed by abolition of p53-dependent 'stress' responses including induction of the cyclin/CDK inhibitor p21WAF1 and G1/S arrest following DNA-damage. In contrast, no change was detected in the phenotype of 'unstressed' clones, with respect to any of the following parameters: proliferation rate in monolayer, serum-dependence for proliferation or survival, tumorigenicity, cellular morphology, or tissue-specific differentiation markers. The K1 line therefore represents a 'neutral' background with respect to p53 function, permitting the derivation of functionally p53 + or - clones which are not only iso-genic but also iso-phenotypic. Such a panel should be an ideal tool with which to test the p53-dependence of cellular stress responses, particularly the sensitivity to potential therapeutic agents, free from the confounding additional phenotypic differences which usually accompany loss of p53 function. The results also further support the hypothesis that p53 mutation alone is not sufficient to drive progression of thyroid cancer to the aggressive anaplastic form. (+info)