Correlation of BRAF V600E mutations and tumor invaseness in papillary thyroid carcinoma

JCEM 2010, 95(9):4197-4205 Basolo et al

Evaluation of the degree of neoplastic infiltration beyond the thyroid capsule remains a unique parameter that can be evaluated by histopathological examination to label a papillary thyroid carcinoma (PTC) of 20 mm or less in size as a pT1 or pT3 tumor. We correlated the BRAF V600E mutation with both clinical-pathological features and the degree of neoplastic infiltration to redefine the reliability of the actual system of risk stratification in a large selected group of PTCs smaller than 20 mm. The presence of BRAF mutations was examined in 1060 PTCs less than 20 mm divided into four degrees of neoplastic infiltration: 1) totally encapsulated; 2) not encapsulated without thyroid capsule invasion; 3) thyroid capsule invasion; and 4) extrathyroidal extension.

The overall frequency of the BRAF V600E mutation was 44.6%. In both univariate and multivariate analyses, BRAF mutations showed a strong association with PTC variants (classical and tall cell), tumor size (11-20 mm), multifocality, absence of tumor capsule, extrathyroidal extension, lymph node metastasis, higher American Joint Commission on Cancer stage, and younger patient age. In PTCs staged as pT1 with thyroid capsule invasion, the frequency of BRAF mutations was significantly higher than in pT1 tumors that did not invade the thyroid capsule (67.3 vs. 31.8%, respectively; P < 0.0001). No statistically significant difference in BRAF alterations was found between pT1 tumors with thyroid capsule invasion and pT3 tumors (67.3 and 67.5%, respectively).

We suggest that evaluation of BRAF status would be useful even in pT1 tumors to improve risk stratification and patient management, although follow-up data are necessary to confirm our speculations


A current “Holy Grail” among thyroidologists is a mechanism to enhance the information obtained by FNA through applying genetic studies to the tissue in the aspirate. BRAF mutations have been associated with adverse outcomes in thyroid cancer in many studies. This report shows that identifying BRAF mutations increases the ability to predict adverse characteristics of a small papillary tumor. Gradual development of this field will likely come in the next few years, and make FNA even more diagnostically decisive than it is at present.