RESUMO
Currently, there is a lack of efficient recurrence prediction methods for papillary thyroid carcinoma (PTC). In this study, we enrolled 202 PTC patients submitted to total thyroidectomy and radioiodine therapy with long-term follow-up (median = 10.7 years). The patients were classified as having favorable clinical outcome (PTC-FCO, no disease in the follow-up) or recurrence (PTC-RE). Alterations in BRAF, RAS, RET, and TERT were investigated (n = 202) and the transcriptome of 48 PTC (>10 years of follow-up) samples was profiled. Although no mutation was associated with the recurrence risk, 68 genes were found as differentially expressed in PTC-RE compared to PTC-FCO. Pathway analysis highlighted a potential role of cancer-related pathways, including signal transduction and FoxO signaling. Among the eight selected genes evaluated by RT-qPCR, SLC2A4 and GADD45B showed down-expression exclusively in the PTC-FCO group compared to non-neoplastic tissues (NT). Increased expression of GADD45B was an independent marker of shorter disease-free survival [hazard ratio (HR) 2.9; 95% confidence interval (CI95) 1.2-7.0] in our cohort and with overall survival in the TCGA dataset (HR = 4.38, CI95 1.2-15.5). In conclusion, GADD45B transcript was identified as a novel prognostic marker candidate in PTC patients treated with total thyroidectomy and radioiodine therapy.
Assuntos
Antígenos de Diferenciação/metabolismo , Biomarcadores Tumorais/metabolismo , Radioisótopos do Iodo/uso terapêutico , Recidiva Local de Neoplasia/patologia , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/mortalidade , Antígenos de Diferenciação/genética , Biomarcadores Tumorais/genética , Terapia Combinada , Feminino , Seguimentos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/metabolismo , Câncer Papilífero da Tireoide/terapia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/terapiaAssuntos
Adenocarcinoma Folicular/cirurgia , Carcinoma Papilar/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/mortalidade , Adenocarcinoma Folicular/patologia , Carcinoma Papilar/patologia , Humanos , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/patologia , Resultado do TratamentoRESUMO
PURPOSE: Anti-thyroglobulin antibodies (TgAb) can be used as a surrogate tumor marker in the follow-up of papillary thyroid carcinoma (PTC). We try to determine if the change in TgAb levels in the first post-operative year is a good predictor of persistence/recurrence risk in TgAb-positive PTC patients. METHODS/PATIENTS: 105 patients with PTC who underwent thyroidectomy between 1988 and 2014 were enrolled. We calculated the percentage of change in TgAb levels with the first measurement at 1-2 months after surgery and the second one at 12-14 months. RESULTS: TgAb negativization was observed in 29 patients (27.6%), a decrease of more than 50% was observed in 57 patients (54.3%), less than 50% in 12 patients (11.4%) and in 7 patients (6.7%) the TgAb level had increased. The percentage of persistence/recurrence was 0, 8.8, 16.7 and 71.4% in each group, respectively (p < 0.001). In the multivariate analysis, only the percentage of change in TgAb showed a significant association with the risk of persistence/recurrence, regardless of other factors such as age, size and TNM stages. CONCLUSIONS: Changes in TgAb levels in the first year after surgery can predict the risk of persistence/recurrence of TgAb-positive PTC patients. Patients who achieved negativization of TgAb presented an excellent prognosis.
Assuntos
Autoanticorpos/sangue , Biomarcadores Tumorais/análise , Carcinoma Papilar/patologia , Recidiva Local de Neoplasia/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/mortalidade , Autoanticorpos/imunologia , Carcinoma Papilar/sangue , Carcinoma Papilar/imunologia , Carcinoma Papilar/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/imunologia , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Testes de Função Tireóidea , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/imunologia , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
BACKGROUND: Preoperative detection of RAS mutations can contribute to cancer risk assessment in indeterminate thyroid nodules, although RAS is not always associated with malignancy. METHODS: Fine-needle aspiration samples classified in 1 of 3 indeterminate cytology categories were prospectively tested for N-, H-, and K-RAS mutations using next-generation sequencing assay. RESULTS: In the study, 93 patients with 94 nodules had preoperative RAS detected, of whom 86 patients had an operation (69% total thyroidectomy, 29% lobectomy). In total, 76% of RAS-positive nodules were malignant and follicular variant papillary thyroid cancer was the most common cancer type (83%). HRAS mutations had the greatest risk of cancer (92%) followed by NRAS (74%) and KRAS (64%; P = .05). No preoperative variables were associated with malignancy including age (P = .07), sex (P = .49), RAS isoform (P = .05), mutational allelic frequency (P = .49), nodule size (P = .14), cytology category (P = .63), or ultrasound bilaterality (P = .24), multifocality (P = .23), or presence of ≥1 suspicious feature (P = .86). Only 60% of patients with a unifocal nodule on ultrasound had single focus low-risk encapsulated follicular variant papillary thyroid cancer or benign disease. CONCLUSION: Preoperative RAS mutation detection in thyroid nodules carries a substantial risk of cancer with a greater risk associated with HRAS and NRAS. Most RAS malignancies are follicular variant papillary thyroid cancer, which may inform the extent of operation.
Assuntos
Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Adulto , Idoso , Biópsia por Agulha Fina , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Prognóstico , Estudos Prospectivos , Medição de Risco , Análise de Sobrevida , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/cirurgia , Tireoidectomia/mortalidade , Resultado do TratamentoRESUMO
OBJECTIVES: To correlate thyroid cancer genotype with histology and outcomes. BACKGROUND: The prognostic significance of molecular signature in thyroid cancer (TC) is undefined but can potentially change surgical management. METHODS: We reviewed a consecutive series of 1510 patients who had initial thyroidectomy for TC with routine testing for BRAF, RAS, RET/PTC, and PAX8/PPARG alterations. Histologic metastatic or recurrent TC was tracked for 6 or more months after oncologic thyroidectomy. RESULTS: Papillary thyroid cancer (PTC) was diagnosed in 97% of patients and poorly differentiated/anaplastic TC in 1.1%. Genetic alterations were detected in 1039 (70%); the most common mutations were BRAFV600E (644/1039, 62%), and RAS isoforms (323/1039, 31%). BRAFV600E-positive PTC was often conventional or tall cell variant (58%), with frequent extrathyroidal extension (51%) and lymph node metastasis (46%). Conversely, RAS-positive PTC was commonly follicular variant (87%), with infrequent extrathyroidal extension (4.6%) and lymph node metastasis (5.6%). BRAFV600E and RET/PTC-positive PTCs were histologically similar. Analogously, RAS and PAX8/PPARG-positive PTCs were histologically similar. Compared with RAS or PAX8/PPARG-positive TCs, BRAFV600E or RET/PTC-positive TCs were more often associated with stage III/IV disease (40% vs 15%, P < 0.001) and recurrence (10% vs 0.7%, P < 0.001; mean follow-up 33 ± 21 mo). Distant metastasis was highest in patients with RET/PTC-positive TC (10.8%, P = 0.02). CONCLUSIONS: In this large study of prospective mutation testing in unselected patients with TC, molecular signature was associated with distinctive phenotypes including cancers, with higher risks of both distant metastasis and early recurrence. Preoperative genotype provides valuable prognostic data to appropriately inform surgery.
Assuntos
Carcinoma/genética , Carcinoma/mortalidade , Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/mortalidade , Adulto , Idoso , Carcinoma/patologia , Carcinoma/cirurgia , Carcinoma Papilar , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Invasividade Neoplásica , Estadiamento de Neoplasias , Fator de Transcrição PAX8 , Fatores de Transcrição Box Pareados/genética , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-ret/genética , Estudos Retrospectivos , Análise de Sobrevida , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Tireoidectomia/mortalidade , Resultado do TratamentoRESUMO
BACKGROUND: We previously demonstrated the clinical utility of using response to therapy variables obtained during the first 2 years of follow-up to actively modify initial risk estimates which were obtained using standard clinic-pathologic staging systems. While our proposed dynamic risk stratification system accurately reclassified patients who demonstrated an excellent response to therapy as low-risk patients, it grouped patients with either biochemical or structural evidence of disease into a single incomplete response to therapy cohort. This cohort included a wide variety of patients ranging from very minor thyroglobulin (Tg) elevations in the absence of structurally identifiable disease to widespread, progressive structural disease. Here we determined whether subdivision of the incomplete response to therapy category more precisely predicted clinical outcomes. We hypothesized that patients with an incomplete response to therapy based on persistently abnormal Tg values alone would have better clinical outcomes than patients having structurally identifiable disease. METHODS: Following total thyroidectomy and radioactive iodine (RAI) ablation, 192 adult thyroid cancer patients were retrospectively identified as having either a biochemical incomplete response (abnormal Tg without structural evidence of disease) or structural incomplete response (structurally identifiable disease with or without abnormal Tg) as the best response to initial therapy within the first 24 months after RAI ablation. Clinical outcomes evaluated included structural disease progression, biochemical disease progression, and overall survival. RESULTS: Sixty-three patients (33%) had a biochemical incomplete response while 129 (67%) had a structural incomplete response. Eleven to 156 months after evaluation of their responses (mean=70 months), patients with structural incomplete response were significantly more likely to have structural evidence of disease at final follow-up (37% vs. 17%, p=0.0004), structural progression (52% vs. 5%, p<0.001), biochemical progression (45% vs. 11%, p<0.001), and death from disease (38% vs. 0%, p<0.0001) than patients demonstrating a biochemical incomplete response. Overall survival was significantly better in patients with either a biochemical incomplete response or a loco-regional structural incomplete response than patients demonstrating a structural incomplete response with distant metastasis (Kaplan-Meier analysis, p<0.0001). CONCLUSIONS: A structural incomplete response to initial therapy is associated with significantly worse clinical outcome than a biochemical incomplete response to therapy.
Assuntos
Biomarcadores Tumorais/sangue , Diferenciação Celular , Tireoglobulina/sangue , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/efeitos adversos , Adenocarcinoma Folicular , Adenoma Oxífilo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Carcinoma , Carcinoma Papilar , Distribuição de Qui-Quadrado , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Radioterapia Adjuvante , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Tireoglobulina/imunologia , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/mortalidade , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Se analizan la historias clínicas de 45 pacientes con diagnóstico histopatológico de cáncer del tiroides en el Hospital Universitario de Maracaibo, en el período comprendido entre 1980 y 1994. 34 pacientes (75,55 por ciento) pertenecieron al sexo femenino y 11 pacientes (24,44) al sexo masculino, con una relción mujer a hombre de 3,09:1. La edad promedio de los pacientes fue de 41 años con un rango de 24 a 50 años. Un porcentaje de los pacientes presentó como consulta una tumoración palpable y deformidad de cuello, perdida de peso y anorexia. Las formas de presentación clínica de la enfermedad más frecuente fueron nódulos solitarios (60,00 por ciento) y nódulos múltiples (37,77 por ciento). La lobectomía total, la tiroidectomía total y la lobectomía parcial fueron las intervenciones quirúrgicas más frecuentemente realizadas. Los tipos histológicos de cáncer de tiroides más frecuentes correspondieron a las variables papilar (62,22 por ciento) y folicular (28,88 por ciento)