RESUMEN
PURPOSE: The BRAF(V600E) mutation represents a novel indicator of the progression and aggressiveness of papillary thyroid carcinoma (PTC). The purpose of this study was to determine the clinical significance of free circulating mutant BRAF(V600E) in predicting the advanced disease of PTC. MATERIALS AND METHODS: Seventy seven matched tumor and plasma samples obtained from patients with both benign and PTC were analyzed for BRAF(V600E) mutation using a peptide nucleic acid (PNA) clamp real-time polymerase chain reaction (PCR). RESULTS: The BRAF(V600E) mutation was absent in tumor DNA samples obtained from patients with benign follicular adenomas or adenomatous goiter. In contrast, 49 of 72 (68.1%) PTC tumors were positive for the BRAF(V600E) mutation. Among them, 3 (6.1%) patients with PTC were positive for BRAF(V600E) mutation in plasma and tumor. However, all 3 patients (100%) had lateral lymph node and lung metastasis. CONCLUSION: These findings suggest that the BRAF(V600E) mutation can be detected using a PNA clamp real-time PCR in the blood of PTC patients with lung metastasis. Future studies are warranted to determine clinical significance of serum BRAF(V600E) mutation in large prospective studies.
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adenocarcinoma Papilar/genética , Carcinoma/genética , Análisis Mutacional de ADN , ADN de Neoplasias/genética , Neoplasias Pulmonares/genética , Ganglios Linfáticos/patología , Metástasis Linfática , Mutación , Invasividad Neoplásica , Estadificación de Neoplasias , Ácidos Nucleicos de Péptidos , Estudios Prospectivos , Proteínas Proto-Oncogénicas B-raf/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Neoplasias de la Tiroides/genéticaRESUMEN
Background: Several molecules that may have a role in tumor proliferation, differentiation and invasion, have been detected in thyroid carcinoma. Some of these molecules are NIS, c-MET, TIMP1 an ephrinB2. Aim: To detect the presence of these molecules in tissue samples of thyroid carcinoma and relate their expression to the biological behavior of the tumor. Material and Methods: Tissue samples were prospectively obtained from 35 patients operated for a papillary thyroid carcinoma. Twelve patients had regional lymph node involvement. NIS, c-MET, TIMP1 and EphrinB2 were detected by real time polymerase chain reaction(RT-PCR) and immunohistochemistry. Results: The expression of markers by RT-PCR was non significantly higher among tumors with lymph node involvement. Immunohistochemistryshowed a significantly lower nuclear expression and a higher cytoplasmatic expression of EphrinB2 in tumors with lymph node involvement. Conclusions: Immunohistochemical expression of EphrinB2 could be useful for the initial staging of papillary thyroid carcinoma.