Lupi C et al. (2007) Association of BRAF V600E mutation with poor clinicopathological outcomes in 500 consecutive cases of papillary thyroid carcinoma. J Clin Endocrinol Metab 92: 4085–4090

Lupi et al. have analyzed the presence of B-Raf mutations in patients with papillary thyroid carcinoma (PTC) and examined the correlation of these mutations with clinico-pathological parameters. Thyroid specimens from 500 consecutive patients, operated on for a PTC at a single center, were retrospectively evaluated. B-Raf mutations were found in 219 cases among which B-Raf Val600Glu was present in 214. Histologically, a high frequency of B-Raf Val600Glu mutations was found in the aggressive, tall-cell variant and in the classical variant of PTC, whereas a low frequency was observed in follicular variants.

Univariate analysis revealed a significant association between the presence of B-Raf Val600Glu mutations and extra-thyroidal invasion, multicentricity, presence of nodal metastases, higher tumor class and the absence of a tumor capsule. By multivariate analysis only the presence of a tumor capsule was statistically associated with a low frequency of B-Raf Val600Glu mutations. The B-Raf Val600Glu mutation was associated with the absence of a tumor capsule in microadenomas and in the follicular variant of PTC. In these two variants the absence of a tumor capsule was associated with larger tumor size. In the follicular-variant encapsulated tumors were associated with rare development of node metastases.

The authors suggest that a low frequency of B-Raf Val600Glu mutations and the presence of a tumor capsule are both indicators of low-risk tumors.