BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas.
Activating point mutations of the BRAF gene have been recently reported in papillary thyroid carcinomas. In this study, we analyzed 320 thyroid tumors and six anaplastic carcinoma cell lines and detected BRAF mutations in 45 (38%) papillary carcinomas, two (13%) poorly-differentiated carcinomas, three (10%) anaplastic carcinomas, and five (83%) thyroid anaplastic carcinoma cell lines but not in follicular, Hürthle cell, and medullary carcinomas, follicular and Hürthle cell adenomas, or benign hyperplastic nodules. All mutations involved a T-->A transversion at nucleotide 1796. In papillary carcinomas, BRAF mutations were associated with older age, classic papillary carcinoma or tall cell variant histology, extrathyroidal extension, and more frequent presentation at stages III and IV. All BRAF-positive poorly differentiated and anaplastic carcinomas contained areas of preexisting papillary carcinoma, and mutation was present in both the well-differentiated and dedifferentiated components. These data indicate that BRAF mutations are restricted to papillary carcinomas and poorly differentiated and anaplastic carcinomas arising from papillary carcinomas. They are associated with distinct phenotypical and biological properties of papillary carcinomas and may participate in progression to poorly differentiated and anaplastic carcinomas.
Nikiforova
Marina N
MN
Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio 45267, USA.
Kimura
Edna T
ET
Gandhi
Manoj
M
Biddinger
Paul W
PW
Knauf
Jeffrey A
JA
Basolo
Fulvio
F
Zhu
Zhaowen
Z
Giannini
Riccardo
R
Salvatore
Giuliana
G
Fusco
Alfredo
A
Santoro
Massimo
M
Fagin
James A
JA
Nikiforov
Yuri E
YE
D000328:Adult; D000368:Aged; D002291:Carcinoma, Papillary / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D015513:Oncogene Proteins / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation; D015995:Prevalence; D048493:Proto-Oncogene Proteins B-raf; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016606:Thyroid Nodule / Q000453:epidemiology / Q000235:genetics / Q000473:pathology
D015513:Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf