BRAF(V600E) mutation is the most frequent genetic alteration in papillary thyroid carcinomas (PTCs) that are 80-90% of all thyroid cancers. We evaluated the relationship between BRAF(V600E) and tumor, host, and environmental factors in PTCs from all geographical areas of Sicily. By PCR, BRAF(V600E) was investigated in a series of 323 PTCs diagnosed in 2002-2005. The correlation between clinicopathological tumor, host, and environmental characteristics and the presence of BRAF(V600E) were evaluated by both univariate and multivariate analyses. BRAF(V600E) was found in 38.6% PTCs, with a 52% frequency in the classical PTCs and 26.4% in the tall cell variant. Univariate analysis indicated that BRAF (V600E) was associated with greater tumor size (P=0.0048), extra-thyroid invasion (P(V600E) was an independent predictor of extra-thyroid invasion (P = 0.0001) and cervical lymph nodal metastasis (P=0.0005). The association between BRAF(V600E) and extra-thyroid invasion was also found in micro-PTCs (P = 0.006). In 60 classical PTCs, BRAF(V600E) was positively correlated with matrix metalloproteinase-9 expression (P = 0.0047), suggesting a possible mechanism for BRAF(V600E) effect on PTC invasiveness. No association was found between BRAF(V600E) and patient age, gender, or iodine intake. In contrast, a strong association was found with residency in Eastern Sicily (P(V600E) mutation is a marker of aggressive disease in both micro- and macro-PTCs. Moreover, for the first time, a possible link between BRAF(V600E) mutation and environmental carcinogens is suggested.
ASJC Scopus subject areas
- Cancer Research
- Endocrinology, Diabetes and Metabolism