RESUMEN
ABSTRACT Objectives: This observational study analyzed telomerase reverse transcriptase (pTERT) mutations in 45 fine-needle aspiration (FNA) specimens obtained from thyroid nodules followed by postoperatively confirmation of papillary thyroid cancer (PTC) diagnosis, examining their relationship with clinicopathologic aspects and the BRAFV600E mutation. Subjects and methods: Clinical information was collected from patients who presented to Ribeirao Preto University Hospital for surgical consultation regarding a thyroid nodule and who underwent molecular testing between January 2010 to October 2012. Tests included a DNA-based somatic detection of BRAFV600E and pTERT mutations. Results: We found coexistence of pTERTC228T and BRAFV600E mutations in 8.9% (4/45) of thyroid nodules. All nodules positive for pTERT mutations were BRAFV600E positives. There was a significant association between pTERTC228T/BRAFV600E with older age and advanced stage compared with the group negative for either mutation. Conclusions: This series provides evidence that FNA is a reliable method for preoperative diagnosis of high-risk thyroid nodules. pTERTC228T/BRAFV600E mutations could be a marker of poor prognosis. Its use as a personalized molecular medicine tool to individualize treatment decisions and follow-up design needs to be further studied.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Neoplasias de la Tiroides/genética , Nódulo Tiroideo/genética , Telomerasa/genética , Proteínas Proto-Oncogénicas B-raf/genética , Cáncer Papilar Tiroideo/genética , Pronóstico , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Análisis Mutacional de ADN , Valor Predictivo de las Pruebas , Factores de Edad , Regiones Promotoras Genéticas/genética , Nódulo Tiroideo/diagnóstico , Nódulo Tiroideo/patología , Biopsia con Aguja Fina , Periodo Preoperatorio , Cáncer Papilar Tiroideo/diagnóstico , Cáncer Papilar Tiroideo/patología , Metástasis Linfática/diagnóstico , Mutación/genética , Estadificación de NeoplasiasRESUMEN
OBJECTIVES: This observational study analyzed telomerase reverse transcriptase (pTERT) mutations in 45 fine-needle aspiration (FNA) specimens obtained from thyroid nodules followed by postoperatively confirmation of papillary thyroid cancer (PTC) diagnosis, examining their relationship with clinicopathologic aspects and the BRAFV600E mutation. SUBJECTS AND METHODS: Clinical information was collected from patients who presented to Ribeirao Preto University Hospital for surgical consultation regarding a thyroid nodule and who underwent molecular testing between January 2010 to October 2012. Tests included a DNA-based somatic detection of BRAFV600E and pTERT mutations. RESULTS: We found coexistence of pTERTC228T and BRAFV600E mutations in 8.9% (4/45) of thyroid nodules. All nodules positive for pTERT mutations were BRAFV600E positives. There was a significant association between pTERTC228T/BRAFV600E with older age and advanced stage compared with the group negative for either mutation. CONCLUSIONS: This series provides evidence that FNA is a reliable method for preoperative diagnosis of high-risk thyroid nodules. pTERTC228T/BRAFV600E mutations could be a marker of poor prognosis. Its use as a personalized molecular medicine tool to individualize treatment decisions and follow-up design needs to be further studied.
Asunto(s)
Proteínas Proto-Oncogénicas B-raf/genética , Telomerasa/genética , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/genética , Nódulo Tiroideo/genética , Adolescente , Adulto , Factores de Edad , Anciano , Biopsia con Aguja Fina , Análisis Mutacional de ADN , Femenino , Humanos , Metástasis Linfática/diagnóstico , Masculino , Persona de Mediana Edad , Mutación/genética , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Periodo Preoperatorio , Pronóstico , Regiones Promotoras Genéticas/genética , Cáncer Papilar Tiroideo/diagnóstico , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Nódulo Tiroideo/diagnóstico , Nódulo Tiroideo/patología , Adulto JovenRESUMEN
BACKGROUND: The inactivation of the tumor-suppressor homeodomain-only protein X (HOPX) usually involves promoter methylation in several cancer types. This study aimed to investigate the HOPX-ß mRNA expression and promoter methylation and their clinical relevance in differentiated thyroid cancer (DTC). PATIENTS AND METHODS: Clinicopathological data and paraffin-embedded thyroid tumor tissues from 21 patients with DTC and 6 with benign tumors (T) and their non-tumor parenchyma (NT) were investigated. Tumor cell lines (FTC238, FTC236 and WRO) were treated with demethylating agent. HOPX-ß mRNA expression was assessed by qRT-PCR and methylation status by Q-MSP. Thyroid cancer data from Cancer Genome Atlas (TCGA) was also collected. RESULTS: HOPX-ß mRNA re-expression in two cell lines treated with demethylating agent was observed concomitantly with reduced promoter methylation. Reduced mRNA expression in T group compared to their NT was observed, and reduced protein expression in T compared to NT was observed in three cases. Low mRNA expression with high methylation status was detected in 6/14 DTC samples. High methylation status was associated with older age at diagnosis, recurrent or progressive disease and with the presence of new neoplasm event post initial therapy while hyper-methylation correlated with worse overall survival, worse disease-free status and older age. CONCLUSION: A moderate coupling of downregulation of HOPX-ß mRNA expression in DTC followed by high HOPX-ß promoter methylation was observed however; high HOPX promoter methylation status was associated with the worse prognosis of DTC patients.