PFKFB2 Promoter Hypomethylation as Recurrence Predictive Marker in Well-Differentiated Thyroid Carcinomas.

Despite the low mortality rates, well-differentiated thyroid carcinomas (WDTC) frequently relapse. BRAF and TERT mutations have been extensively related to prognosis in thyroid cancer. In this study, the methylation levels of selected CpGs (5-cytosine-phosphate-guanine-3) comprising a classifier, previously reported by our group, were assessed in combination with BRAF and TERT mutations. We evaluated 121 WDTC, three poorly-differentiated/anaplastic thyroid carcinomas (PDTC/ATC), 22 benign thyroid lesions (BTL), and 13 non-neoplastic thyroid (NT) tissues. BRAF (V600E) and TERT promoter (C228T and C250T) mutations were tested by pyrosequencing and Sanger sequencing, respectively. Three CpGs mapped in PFKFB2, ATP6V0C, and CXXC5 were evaluated by bisulfite pyrosequencing. ATP6V0C hypermethylation and PFKFB2 hypomethylation were detected in poor-prognosis (PDTC/ATC and relapsed WDTC) compared with good-prognosis (no relapsed WDTC) and non-malignant cases (NT/BTL). CXXC5 was hypomethylated in both poor and good-prognosis cases. Shorter disease-free survival was observed in WDTC patients presenting lower PFKFB2 methylation levels (p = 0.004). No association was observed on comparing BRAF (60.7%) and TERT (3.4%) mutations and prognosis. Lower PFKFB2 methylation levels was an independent factor of high relapse risk (Hazard Ratio = 3.2; CI95% = 1.1⁻9.5). PFKFB2 promoter methylation analysis has potential applicability to better stratify WDTC patients according to the recurrence risk, independently of BRAF and TERT mutations.

BEHAVIOUR OF EARLY THYROGLOBULIN AFTER TOTAL THYROIDECTOMY FOR DIFFERENTIATED THYROID CANCER.

CONTEXT: The objectives of treatment of thyroid carcinoma include hormonal suppression, radioiodine ablation and follow-up with serum thyroglobulin (Tg). Tg levels should not be measured before six weeks post-thyroidectomy. OBJECTIVE: To describe the behaviour of early postoperative Tg in patients who underwent total thyroidectomy and its ability to predict the serum Tg levels after suppression. DESIGN: This is a retrospective cohort study. SUBJECTS AND METHODS: Adult patients who underwent total thyroidectomy with at least two postoperative measurements of serum Tg, negative TgAb and concomitant serum TSH values were included. Tg, TgAb and TSH level measurements were completed two weeks postoperatively and during the follow-up period. RESULTS: Twenty-nine patients fulfilled all criteria. The median serum Tg level at two weeks after surgery was 3.8 ug/L (0.3 -300) with a serum TSH level of 69.9 mU/L; 11-227. At the two-week measurement, 16 (55%) patients had serum Tg levels lower than 5 ug/L and 4 patients had levels between 5-10 µg/L. CONCLUSIONS: Postoperative early serum Tg could be an alternative to values measured six months after surgery and could be used as a predictive tool to make earlier therapeutic decisions.

Cáncer tiroideo recurrente: Diagnostico, tratamiento y riesgo de supervivencia

Antecedentes: el 8 al 23 % de los pacientes con CDT, sufre una recurrencia. Dos tercios, dentro de los 10 años. Sin embargo, la mayoría tiene buena supervivencia. Objetivo: analizar los factores de riesgo de supervivencia del CDT recidivado, tras su tratamiento. Diseño: Retrospectivo. Observacional. Lugar de aplicación: Hospital Público de atención terciaria de tumores. Población: 114 pacientes, con una edad media 58,31 y una relación: 2.1 hombres por cada mujer. El 81.5% era de histología papilar, 12.2% folicular. En 44/114 de la serie propia, se efectuó tiroidectomía total extendida al cuello en el 27.2% y a la traquea en 6.8%. En los 70 restantes, el 50% recibió tiroidectomías < que total, el 48.6 % total, extendida al cuello en el 11.7%, y a la traquea en el 5.8%. Métodos: El estudio endoscópico más frecuente fue la telelaringoscopía, seguida por la fíbrobroncoscopía y la fíbroendoscopía digestiva alta. Entre las imágenes, las más utilizadas fueron la tomografia computada, seguida por la ecografía, la resonancia nuclear y el rastreo corporal. El 24.5% de los paciente sufría un cáncer recidivado localmente invasivo. La cirugía de la recurrencia se extendió a los ganglios del cuello en el 94.7%, a la vía aérea en 10.5%, a los músculos en 7.9% y fue solo local en 5.2%. En 35 pacientes se completó la tiroidectomía a la cirugía cervical. Resultados: La cirugía produjo complicaciones en 28 -24.5%, encabezadas por hipocalcemia en 16. Se registraron 11 secuelas, predominando hipocalcemia definitiva en 6 y parálisis recurrencial en 3. 14/114-12.2% - habían sufrido > de 1 recurrencia. En el multivariado, fueron significativos la edad a favor de los <45 años y las neoplasias bien diferenciadas con p: 0.007 y 0.005 respectivamente. La supervivencia a 5 años fue del 70%. Conclusiones: La morbilidad de la cirugía fue mayor. La edad <45 años y la histología bien diferenciada han tenido mejor comportamiento que su opuesta. La supervivencia a 5 años fue del 70%.(AU)

Background: 8 to 23% of patients suffering CDT have a recurrence. Two third parties in the following 10 years after treatment. However, large part of patients have good survival. Objective: to analize risk factors of survival in recurred CDT after treatment. Design: Retrospective - Observational. Setting: Public tertiary care head and neck referral center. Population: 114 patients with mean age 58.31 years old and 2.1 men by each one woman. 81.5% was papillary and 12.2% follicular carcinoma. In 44/114 of own serie, a total thyroidectomy was performed, extended to de lateral neck in 27.26% and trachea in 6.8%. In the rest, 50% received thyroidectomy less than total, 48.5% total thyroidectomy extended to the lateral neck in 11.7% and the trachea in 5.8%. Methods: More frequent endoscopy was telelaryngoscopy followed by fibrobronchoscopy and high digestive endoscopy. Computed tomography, magnetic resonance and 131I scanning were images frequently used. 24.5% of patients had a recurrent locally invasive carcinoma. Surgery of recurrence was extended to cervical nodes in 94.7%, to high respiratory tract in 10.5%, to the muscles in 7.9% and it was only local in 5.2%. In 35 patients thyroidectomy was completed. Results: Surgery was accompanied of 24.5% complications, specially hipocalcemia in 16. 11 sequelas were reported , specially definitive hipocalcemia in 6 and recurrent laryngeal nerve paralysis in 3. 14/114 had more than 1 recurrence. In multivariate analysis age<45 years old and well-differentiated neoplasias were statiscally significative with p: 0.007 and 0.005 respectively. Survival was 70% a 5 years. Conclusions: Morbility of surgery was higher. Age<45 years old and well differentiated histology had better outcome. 5 years survival was 70%.(AU)