Reduction of false-negative papillary thyroid carcinomas by the routine analysis of BRAF(T1799A) mutation on fine-needle aspiration biopsy specimens: a prospective study of 814 thyroid FNAB patients.

OBJECTIVES: To evaluate prospectively the usefulness of the routine determination of BRAF(T1799A) mutation on thyroid fine-needle aspiration biopsy (FNAB) to detect cytopathology false negative papillary thyroid carcinomas (PTC) and, therefore, as a tool to improve the sensitivity of the preoperative cytopathological diagnosis of PTC in thyroid nodules. BACKGROUND: FNAB is the most reliable diagnostic test to discriminate between malignant and benign thyroid nodules, but nondiagnostic results remain a clinical management dilemma. BRAF(T1799A) mutation is the most prevalent genetic alteration in thyroid cancers and is specific for PTC, characteristics that make it the most potentially helpful genetic tool to improve the diagnostic accuracy of FNAB. METHODS: An exhaustive recruitment of all patients subjected to thyroid FNAB in our institution during 4 years was performed. BRAF(T1799A) mutation was determined on thyroid FNAB specimens by PCR and restriction fragment length polymorphism, plus direct sequencing in positive samples. RESULTS: BRAF(T1799A) mutation on FNAB detected 47.2% (17/36) of PTC cases. It confirmed preoperatively 45.5% (5/11) of the PTC cases in the indeterminate category and decreased the rate of cytopathology false-negatives in 33.3% (6/18), improving the combined (BRAF(T1799A) mutation + cytopathological analysis) sensitivity of the detection of PTC on FNAB in 16.7%. CONCLUSIONS: BRAF(T1799A) mutation improves the diagnosis of PTC on FNAB, mainly because of the detection of cytopathology false-negatives, and it can be helpful in the routine analysis of thyroid nodules, especially in clinical settings with moderate sensitivity to detect PTC on FNAB.

Presencia de la mutación BRAF T1799A en el tumor primario como indicador de riesgo, recidiva o persistencia de carcinoma papilar de tiroides / BRAF T1799. A mutation in the primary tumor as a marker of risk, recurrence, or persistence of papillary thyroid carcinoma

Antecedentes y objetivo. La mutación BRAFT1799A se ha relacionado con características tumorales de más agresividad, recidiva tumoral y persistencia de carcinoma papilar de tiroides (CPT), aunque no todos los estudios apoyan esta asociación. En éste, se analiza la asociación entre la presencia de la mutación BRAFT1799A en el tumor primario de pacientes con CPT y las características clinicopatológicas de riesgo, recidiva y persistencia tumoral. Pacientes, material y método. Hemos seguido a 97 pacientes intervenidos de CPT durante una mediana de 64,1 meses. La mutación BRAFT1799A se determinó en ácido desoxirribonucleico procedente de muestras de la tiroidectomía inicial mediante amplificación por PCR del exón 15 del gen braf y análisis de los fragmentos de restricción con la enzima TspRI. Los casos positivos fueron confirmados por secuenciación. La asociación estadística entre la mutación BRAFT1799A y las diferentes variables se estudió mediante los correspondientes tests de contraste de hipótesis más regresión logística. Resultados. El 46,4% de los pacientes eran positivos para la mutación BRAFT1799A. Tras análisis bivariante y multivariante, la mutación BRAFT1799A sólo se asociaba con edad superior a 60 años (odds ratio [OR] = 5,5; intervalo de confianza [IC] del 95%, 1,4-21,9; p=0,019) y tamaño de 1cm o superior (OR=3,6; IC del 95%, 1,2-10,3; p=0,016). No se asociaba con subtipos histológicos, metástasis, recidiva, necesidad de nuevos tratamientos ablativos con I131 o de otras intervenciones quirúrgicas debidas a la aparición de metástasis o persistencia de enfermedad al final del seguimiento. Conclusiones. La mutación BRAFT1799A está asociada a edad superior a 60 años y tamaño tumoral de 1cm o mayor, pero no con otras características clinicopatológicas, recidiva tumoral o persistencia de enfermedad (AU)

Background and objective. The BRAFT1799A mutation is reported to be associated to aggressive, persistent, and recurrent tumor in papillary thyroid carcinoma (PTC) patients. Association of the BRAFT1799A mutation in the primary tumor with the clinicopathological characteristics of PTC patients was analyzed. Patients, material and methods. Ninety-seven PTC patients were followed up for a median of 64.1 months. The BRAFT1799A mutation was analyzed in DNA from initial thyroidectomy biopsies by PCR amplification and restriction fragment length polymorphism using TspRI enzyme. Positive cases were confirmed by DNA sequencing. Statistical association between BRAFT1799A mutation and clinicopathological characteristics was analyzed by the relevant hypothesis tests and logistic regression. Results. 46.4% of patients were positive for the BRAFT1799A mutation. Bivariate and multivariate analysis showed the BRAFT1799A mutation to be only associated to age over 60 years (odds ratio [OR] = 5.5; 95% confidence interval [CI],1.4-21.9; p=0.019) and to tumor size of 1cm or greater (OR=3.6, 95% CI, 1.2-10.3; p=0.016). The BRAFT1799A mutation was not associated to histological subtype, metastasis, recurrence, more aggressive treatments (ablative I131 therapy or surgery), or PTC persistence at the end of follow-up. Conclusions. The BRAFT1799A mutation is associated to age over 60 and a tumor size of 1cm or greater, but not to other clinicopathological characteristics, tumor recurrence or PTC persistence (AU)

[BRAF(T1799A) mutation in the primary tumor as a marker of risk, recurrence, or persistence of papillary thyroid carcinoma]. / Presencia de la mutación BRAF(T1799A) en el tumor primario como indicador de riesgo, recidiva o persistencia de carcinoma papilar de tiroides.

BACKGROUND AND OBJECTIVE: The BRAF(T1799A) mutation is reported to be associated to aggressive, persistent, and recurrent tumor in papillary thyroid carcinoma (PTC) patients. Association of the BRAF(T1799A) mutation in the primary tumor with the clinicopathological characteristics of PTC patients was analyzed. PATIENTS, MATERIAL AND METHODS: Ninety-seven PTC patients were followed up for a median of 64.1 months. The BRAF(T1799A) mutation was analyzed in DNA from initial thyroidectomy biopsies by PCR amplification and restriction fragment length polymorphism using TspRI enzyme. Positive cases were confirmed by DNA sequencing. Statistical association between BRAF(T1799A) mutation and clinicopathological characteristics was analyzed by the relevant hypothesis tests and logistic regression. RESULTS: 46.4% of patients were positive for the BRAF(T1799A) mutation. Bivariate and multivariate analysis showed the BRAF(T1799A) mutation to be only associated to age over 60years (odds ratio [OR] = 5.5; 95% confidence interval [CI],1.4-21.9; p=0.019) and to tumor size of 1cm or greater (OR=3.6, 95% CI, 1.2-10.3; p=0.016). The BRAF(T1799A) mutation was not associated to histological subtype, metastasis, recurrence, more aggressive treatments (ablative I(131) therapy or surgery), or PTC persistence at the end of follow-up. CONCLUSIONS: The BRAFT1799A mutation is associated to age over 60 and a tumor size of 1cm or greater, but not to other clinicopathological characteristics, tumor recurrence or PTC persistence.