High prevalence of BRAF mutation in a Brazilian cohort of patients with sporadic papillary thyroid carcinomas: correlation with more aggressive phenotype and decreased expression of iodide-metabolizing genes.

Although several studies undoubtedly demonstrated that BRAF mutation is an important genetic event in the pathogenesis of papillary thyroid carcinoma (PTC), its prognostic significance and correlation with less differentiated states remains unclear. It has been suggested that the discrepancy may be at least partially due to the insufficient number of cases analyzed, epidemiologic factors, and a combination of different variants of PTC included in these studies. In this context, the prevalence of the BRAF mutation in a Brazilian cohort of PTCs (n = 120) was first assessed and correlated with clinicopathologic features. The BRAF exon 15 mutation was evaluated by direct sequencing. Furthermore, using quantitative polymerase chain reaction, the issue of whether the expression level of the iodide-metabolizing genes (NIS and TSHR) was correlated with BRAF mutational status was investigated. A high prevalence of the BRAF mutation was found in PTC cases (48%). The BRAF mutation was found to be significantly associated with the classic variant of PTC (66%; P < .0001), although it was found in the follicular variant as well (21%). Subtype stratification demonstrated that the BRAF V600E mutation was associated with tumor size, extrathyroid invasion, the presence of lymph node metastasis and risk of disease recurrence, and mortality in patients with the classic variant of PTC. Moreover, the expression levels of NIS and TSHR were remarkably lower in PTCs harboring the BRAF V600E mutation. These findings provide further evidence that BRAF might be associated with a more aggressive phenotype and less differentiated state due to decreased expression of iodide-metabolizing genes. The search for a BRAF mutation in the current study population appears to be valuable for predicting prognosis and guiding management in patients with PTC.

Oler G ，Cerutti JM 《CANCER》

BRAF mutation associated with other genetic events identifies a subset of aggressive papillary thyroid carcinoma.

Costa AM ，Herrero A ，Fresno MF ，Heymann J ，Alvarez JA ，Cameselle-Teijeiro J ，García-Rostán G ... -  《-》

Correlation between B-RAFV600E mutation and clinico-pathologic parameters in papillary thyroid carcinoma: data from a multicentric Italian study and review of the literature.

Fugazzola L ，Puxeddu E ，Avenia N ，Romei C ，Cirello V ，Cavaliere A ，Faviana P ，Mannavola D ，Moretti S ，Rossi S ，Sculli M ，Bottici V ，Beck-Peccoz P ，Pacini F ，Pinchera A ，Santeusanio F ，Elisei R ... -  《ENDOCRINE-RELATED CANCER》

Clinicopathologic features and BRAF(V600E) mutation analysis in cutaneous metastases from well-differentiated thyroid carcinomas.

Cutaneous metastases from well-differentiated thyroid carcinomas are rare and are usually identified in patients with widely disseminated disease. Occasionally, thyroid carcinomas can present as cutaneous metastases for which the primary site needs to be determined. Papillary thyroid carcinomas (PTCs) commonly have BRAF(V600E) mutation. A series of 16 cutaneous metastases were analyzed from well-differentiated thyroid carcinomas to learn more about the clinicopathologic features and BRAF(V600E) mutation status. Eleven cases of PTC and 5 of follicular thyroid carcinoma (FTC) metastatic to the skin were evaluated. All cutaneous metastases were studied histologically and with thyroglobulin and thyroid transcription factor immunostains. All tumor samples were analyzed for mutations at nucleotide 1799 in exon 15 of the BRAF gene. Two patients with FTC presented with cutaneous metastases. Fourteen of 16 patients died of disease and 2 were alive with disease at follow-up. The histologic features of the cutaneous metastases were generally characteristic of the primary tumor; however, 2 of the 11 PTC metastases demonstrated cytoplasmic clearing not typical of classic PTC. BRAF(V600E) mutation (T1799A) was detected in 5 of 11 cases of PTC and in none of the 5 FTCs. Cutaneous metastases from PTC may show prominent clear cell change requiring differentiation from clear cell hidradenoma, clear cell dermatofibroma, malignant melanoma with prominent clear cell change, and cutaneous metastasis from renal cell carcinoma. BRAF(V600E) mutation is identified in a subset of cutaneous metastases from PTC. Cutaneous metastases from PTC and FTC are associated with a very poor prognosis.

Erickson LA ，Jin L ，Nakamura N ，Bridges AG ，Markovic SN ，Lloyd RV ... -  《-》

The BRAFV600E oncogene induces transforming growth factor beta secretion leading to sodium iodide symporter repression and increased malignancy in thyroid cancer.

Riesco-Eizaguirre G ，Rodríguez I ，De la Vieja A ，Costamagna E ，Carrasco N ，Nistal M ，Santisteban P ... -  《-》