Immunohistochemical and Molecular Analyses Focusing on Mesenchymal Cells in Papillary Thyroid Carcinoma with Desmoid-Type Fibromatosis.
PATHOBIOLOGY(2018)
摘要
Objective: This study was designed to evaluate the prevalence of CTNNB1 (-catenin) mutations in cases of papillary thyroid carcinoma with desmoid-type fibromatosis (PTC-DTF) expressing aberrant nuclear and cytoplasmic immunoreactivity for -catenin. Methods: Eight cases of PTC-DTF were available for this study. Immunohistochemistry for -catenin and BRAF(V600E) was performed. CTNNB1 and BRAFV600E mutations were also evaluated by direct sequencing. Results: For -catenin, although we could demonstrate aberrant nuclear and cytoplasmic immunoreactivity in DTF components in all cases, suggesting activated Wnt signaling, direct sequencing revealed a missense mutation, c.121A>G (p.T41A), in exon 3 in only one case, and no mutations in exons 3, 4, and 5 in the other cases. In the BRAF(V600E) analyses, immunohistochemistry revealed positive staining in the carcinoma cells but not DTF components of all cases. These findings were subsequently validated by direct sequencing. Conclusion: This study suggests the significance of the BRAFV600E mutation and activation of Wnt signaling pathway in the carcinoma cells and DTF components, respectively. We believe that the CTNNB1 mutations are not the major factor behind -catenin translocation indicating Wnt pathway activation. Further study is required to evaluate whether molecular abnormalities other than the CTNNB1 mutation cause activation of Wnt signaling in DTF components of PTC-DTF.
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关键词
Papillary thyroid carcinoma,Desmoid-type fibromatosis,-Catenin,CTNNB1,BRAF(V600E)
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