Lopez-Campistrous A, et al. - In papillary thyroid carcinomas with (n=182) and without (n=303) nodal metastases, the researchers investigated thyroid transcription factor 1 (TTF1) nuclear expression in relation to adverse pathological characteristics, disease recurrence, and BRAF status, since the function of the thyroid follicular cell, depends on the nuclear expression of TTF1. In approximately 73%, the overall nuclear expression level of TTF1 was powerful and diffuse whereas 27% displayed lower levels or a paucity of nuclear staining. Approximately 59% demonstrated the BRAF mutation, in the same cohort. Low levels of TTF1 nuclear expression was associated with vascular invasion, extrathyroidal extension, and nodal metastases, on univariate analysis. Low levels of TTF1 were most powerfully related to nodal metastases and vascular invasion as exhibited by multivariate analysis. TTF1 levels were not correlated to the BRAF mutation. TTF1 staining alone prognosticated disease recurrence, however, when combined with BRAF status, the 2 markers manifested a more marked impact. Very low levels of disease recurrence were presented by subjects lacking the BRAF mutation and exhibiting normal levels of TTF1. Conversely, in 31% of cases in the same time frame, recurrence of subject tumors with low levels of TTF1 and the BRAF mutation was noted. The mixed expression of BRAF under varying levels of differentiation may be described, in part, the contradictory studies about the influence of BRAF mutations on subject prognosis and also showed a complex genomic signature for dedifferentiated thyroid cancer.