BRAFV600E MUTATION IS A BAD PROGNOSTIC FACTOR BOTH FOR THE OUTCOME AND SURVIVAL OF PAPILLARY THYROID CANCER PATIENTS

Viola D.¹, Ugolini C.², Lupi C.², Biagini A.¹, Giannini R.², Romei C.¹, Miccoli P.³, Pinchera A.¹, Basolo F.², Rossella E.¹

¹Department of Endocrinology, Azienda-Ospedaliero Universitaria Pisana, Pisa, Italy, ²Department of Oncology, Azienda-Ospedaliero Universitaria Pisana, Pisa, Italy, ³Department of Surgery, Azienda-Ospedaliero Universitaria Pisana, Pisa, Italy

Abstract

BRAFV600E mutation and RET/PTC rearrangements are the most frequent genetic alterations (40% and 25% respectively) in papillary thyroid carcinoma (PTC). While the prognostic role of RET/PTC rearrangements has been excluded, a relationship between BRAFV600E mutation and a bad prognosis has been reported in some studies but not confirmed in others. The short term follow up of the analysed series represents the major limit of these studies. We investigated the clinical-pathological features associated with the BRAFV600E mutation and its prognostic value in a large series of PTC with a mean follow-up of 15 years. We studied 102 patients with PTC diagnosed between 1985 and 1992 and actively followed in our Department. BRAFV600E mutation was evaluated by PCR-SSCP and direct-sequencing. The correlation between the presence/absence of the BRAFV600E mutation, clinical-pathological features and outcome of PTC patients was evaluated. Thirty-eight PTC (37.3%) harbored a BRAFV600E mutation. The correlation between the clinical-pathological features of PTC and BRAFV600E mutation showed that the genetic alteration was more frequent in patients older than 60 years (p=0.02) and in cases with an advanced stage (p=0.005). A worse outcome of PTC patients was significantly correlated with several parameters (age at diagnosis, tumor size, lymph-node metastases, extrathyroid extension, distant metastases, and advanced clinical class), and also with the BRAFV600E mutation. However, when the multivariate analysis was performed, only the BRAFV600E mutation showed an independent correlation (p=0.03). In addition, the survival curve of PTC patients with BRAFV600E mutation was significantly lower than that of not mutated cases (p=0.015). In conclusion, our study demonstrated that the BRAFV600E mutation is an independent bad prognostic factor both for the outcome and survival of PTC patients. This finding suggests that the molecular characterization of the thyroid tumor could be useful in the clinical practice to plan a more aggressive therapy and follow up.