RESUMEN
BACKGROUND: The feasibility of using molecular genetic markers for the diagnosis of thyroid tumors and the impact on the prognosis of thyroid cancer are being actively investigated. The most interesting are genes, the detection of which is associated not only with thyroid cancer, but also with a more aggressive course of the disease. The ability to diagnose the molecular profile of minimally invasive methods with the study of freely circulating DNA tumor tissue in blood plasma is a modern trend of medicine. AIMS: to evaluate the frequency of somatic mutations in the «hot spots» of BRAF, KRAS, KRAS, EIF1AX and TERT genes in circulating DNA of blood plasma. MATERIALS AND METHODS: Samples of DNA, extracted from the removed tumor and non-tumor thyroid tissue, were tested for the presence of somatic mutations in hot spots of the genes BRAF, KRAS, NRAS, TERT, and EIF1AX and then in identifying mutations and testing appropriate samples of free circulating DNA in blood plasma. RESULTS: mutations in the» hot spots «of the BRAF gene (exon 15, codon area 600-601) were found in 54 patients, mutations in the» hot spots « of the NRAS gene (exon 3, codon 61) – in 12 patients; mutations in the hot spots of the KRAS, TERT and EIF1AX genes were not detected. In freely circulating blood plasma DNA, BRAF gene mutations were detected in 1 case, NRAS gene mutations were detected in 1 case. CONCLUSIONS: the use of freely circulating DNA of blood plasma in the testing of the studied sample did not show the feasibility for the diagnosis of thyroid tumors.
Asunto(s)
Ácidos Nucleicos Libres de Células , Neoplasias de la Tiroides , ADN , Humanos , Plasma , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias de la Tiroides/diagnósticoRESUMEN
CONTEXT: Papillary thyroid carcinoma (PTC) in patients exposed to environmental radioiodine after the Chernobyl accident is thought to have a relatively aggressive clinical course. Long-term results of treatment are not well known, especially in comparison with sporadic PTC. OBJECTIVE: The determination of risk factors for PTC recurrence in a controlled for baseline factors group of patients with radiation-related and sporadic PTC. DESIGN: Retrospective cohort study involving patients treated for PTC and followed-up in 1991-2008. Risk factors were assessed by stratified analysis using the proportional hazard model. SETTING: Referral center-based. PATIENTS: A total of 497 patients were enrolled. Patients exposed to radioiodine were 172 individuals with reconstructed individual radiation thyroid doses ranging 51-3170 mGy. Patients with sporadic PTC included 325 individuals matched to exposed patients for sex, age ± 5 yr and time to treatment ± 2 yr. MAIN OUTCOME MEASURE: Cancer recurrence. RESULTS: Nodal disease increased the recurrence rate (HR = 5.21; 95% CI = 1.63-16.7) while the presence of tumor capsule (HR = 0.17; 95% CI = 0.06-0.45) and, particularly, treatment according to the Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer significantly reduced it (HR = 0.16; 95% CI = 0.06-0.42). None of the tested variables interacted with radiation factor. CONCLUSIONS: PTC developing after internal exposure to radioiodine does not display specific risk factors for recurrence different from those in sporadic PTC. Common treatment approaches for patients with PTC should be recommended regardless of a history of radiation exposure.
Asunto(s)
Carcinoma Papilar/epidemiología , Accidente Nuclear de Chernóbil , Radiación , Neoplasias de la Tiroides/epidemiología , Adolescente , Adulto , Edad de Inicio , Carcinoma Papilar/patología , Carcinoma Papilar/terapia , Niño , Estudios de Cohortes , Supervivencia sin Enfermedad , Determinación de Punto Final , Estudios de Seguimiento , Humanos , Radioisótopos de Yodo/uso terapéutico , Escisión del Ganglio Linfático , Recurrencia Local de Neoplasia , Neoplasias Inducidas por Radiación/epidemiología , Factores de Riesgo , Federación de Rusia/epidemiología , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/terapia , Tiroidectomía , Tirotropina/antagonistas & inhibidores , Adulto JovenRESUMEN
The study investigated an association between the germline polymorphism at TP53 codon 72 and the development of papillary thyroid cancer (PTC) following exposure to radiation from the Chernobyl accident. TP53 genotype was examined in 48 pediatric/adolescent (age at diagnosis <18 years) and 68 adult post-Chernobyl patient with PTC, 53 adult patients with sporadic PTC and 313 healthy individuals from Russian-Ukrainian population. In addition, we evaluated loss of heterozygosity for TP53 and the allele expression ratio. The genotype of the patients was correlated with clinicopathological data. Arg TP53 homozygotes were found to be significantly underrepresented among adults with post-Chernobyl PTC, but not in children and adolescents when compared with sporadic PTC cases and the general population. In the tumors, cell transformation did not lead to allelic loss or biased TP53 allele expression in heterozygous individuals. None of TP53 genotypes specifically associated with tumor stage and morphology, however there were particular correlations with lymph node status in certain age groups of radiation-associated cases not seen in sporadic PTCs. The findings suggest TP53 allele combinations other than Arg/Arg may contribute to the risk of development of PTC in individuals exposed to radiation during their late childhood, adolescence or in young adulthood.
Asunto(s)
Carcinoma Papilar/patología , Neoplasias Inducidas por Radiación/patología , Polimorfismo Genético/genética , Neoplasias de la Tiroides/patología , Proteína p53 Supresora de Tumor/genética , Adolescente , Adulto , Anciano , Alelos , Secuencia de Bases , Carcinoma Papilar/genética , Niño , Preescolar , Codón/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Frecuencia de los Genes , Genotipo , Humanos , Lactante , Recién Nacido , Pérdida de Heterocigocidad , Metástasis Linfática , Masculino , Persona de Mediana Edad , Mutación Missense/genética , Mutación Missense/efectos de la radiación , Estadificación de Neoplasias , Neoplasias Inducidas por Radiación/genética , Polimorfismo Genético/efectos de la radiación , Neoplasias de la Tiroides/genéticaRESUMEN
Spindle epithelial tumor with thymus-like differentiation (SETTLE) is an extremely rare type of thyroid tumor. It has been reported only 20 times in the English literature. This tumor occurs predominantly in young patients and has a protracted clinical course despite the occurrence of metastases. In the recent literature SETTLE has been considered to be a tumor of low malignant potential with distant metastases developing some years after diagnosis. Herein we report a case of SETTLE in a 22-yr-old man in which a lymph node metastasis developed soon after the primary tumor manifestation. Histological examination of the tumor showed the predominantly monophasic variant of SETTLE. The primary and metastatic lesions were highly cellular tumors composed of sheets of spindle cells that were positive for pan-cytokeratin and vimentin and negative for thyroglobulin, calcitonin, and S-100 protein.
Asunto(s)
Metástasis Linfática/patología , Neoplasias Glandulares y Epiteliales/secundario , Timo/patología , Neoplasias de la Tiroides/patología , Adulto , Humanos , Inmunohistoquímica , Escisión del Ganglio Linfático , Masculino , Cuello/patología , Neoplasias Glandulares y Epiteliales/metabolismo , Neoplasias de la Tiroides/metabolismoRESUMEN
Paired DNA samples of tumor and normal thyroid tissue from adult patients possibly exposed to radioactive Chernobyl fallout [11 cases of papillary thyroid carcinoma (PTC) and 6 follicular adenomas] and from control samples (9 PTC occurring in Japanese patients) were examined for the relative mitochondrial DNA (mtDNA) content, prevalence and level of common deletion (CD), and large-scale deletions in mtDNA. Elevated relative mtDNA content as estimated by real-time PCR was found in tumor tissue in most cases, but no significant correlation with the level of radioiodine contamination of patients' residency nor with clinicopathological data were found. CD was detected in every DNA specimen from all types of tissue regardless of the presence of oxyphillic cell changes. Elevated level of the CD was predominantly found in tumor tissue of the radiation-associated group but not in sporadic PTC. No correlation was noted with clinicopathological parameters, radioiodine contamination, and relative mtDNA content. The quantity of large-scale deletions in mtDNA was elevated in most tumor tissues, especially in the radiation-associated group and tended to correlate with the level of radiopollutant in PTC. In contrast to sporadic PTC, highly significant-positive correlation between the presence of large scale mtDNA deletions and relative mtDNA content was found in radiation-associated tumors (P = 0.001 and P = 0.019 in PTC and follicular adenoma, respectively). Normal tissue displayed the inverse tendency. No association with level of the CD was found in either group of cases. Concordant increase of both relative mtDNA content and number of mtDNA deletions was detected more often in radiation-associated PTC than in sporadic PTC. Thus, simultaneous determination of the number of large-scale mtDNA deletions and relative mtDNA content may be useful to elucidate molecular distinctive features of radiation-associated thyroid tumors.