Title | BRAF(V600E) mutation and the biology of papillary thyroid cancer. |
Publication Type | Journal Article |
Year of Publication | 2008 |
Authors | Frasca F, Nucera C, Pellegriti G, Gangemi P, Attard M, Stella M, Loda M, Vella V, Giordano C, Trimarchi F, Mazzon E, Belfiore A, Vigneri R |
Journal | Endocr Relat Cancer |
Volume | 15 |
Issue | 1 |
Pagination | 191-205 |
Date Published | 2008 Mar |
ISSN | 1351-0088 |
Keywords | Carcinoma, Papillary, Disease Progression, DNA Primers, Female, Follow-Up Studies, Geography, Humans, Immunoenzyme Techniques, Lasers, Lymphatic Metastasis, Male, Matrix Metalloproteinase 9, Microdissection, Middle Aged, Mutation, Neoplasm Invasiveness, Proto-Oncogene Proteins B-raf, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, Sicily, Thyroid Neoplasms |
Abstract | 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<0.0001), and cervical lymph nodal metastases (P=0.0001). Multivariate logistic regression analysis confirmed that BRAF((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<0.0001 compared with Western Sicily). These results indicate that BRAF((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. |
DOI | 10.1677/ERC-07-0212 |
Alternate Journal | Endocr Relat Cancer |
PubMed ID | 18310287 |
Related Faculty:
Massimo Loda, M.D.