Journal
VIRCHOWS ARCHIV
Volume 469, Issue 6, Pages 687-696Publisher
SPRINGER
DOI: 10.1007/s00428-016-2027-5
Keywords
Papillary carcinoma; Thyroid; TERT; BRAF; Telomere maintenance
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The prognostic value of BRAF (V600E) and TERT promoter mutation in papillary thyroid carcinoma (PTC) is controversial. We examined alterations in BRAF (V600E) and TERT promoter by PCR-direct sequencing in PTC of 144 Japanese patients. Alternative lengthening of telomeres was examined as another mechanism of telomere maintenance by immunohistochemical staining for ATRX and DAXX. Of the clinicopathological characteristics, regional lymph node metastasis, extra-thyroid extension, multifocality/intrathyroidal spread, and advanced stage (III/V) were associated with shorter disease-free survival rate (DFSR). TERT promoter mutation was found in eight patients (6 %), and this was significantly associated with total thyroidectomy, multifocality/intrathyroidal spread, lymph node metastasis and advanced stage. The BRAF (V600E) mutation was found in 53 patients (38.2 %) but was not associated with any clinicopathological factors. TERT mutations were not correlated with BRAF (V600E) mutation status. TERT mutation-positive tumors (TERT+) showed lower DFSR than BRAF (V600E) -mutation-positive tumors (BRAF (V600E) +), and TERT+/BRAF (V600E) + tumors showed lower DFSR than BRAF (V600E) + tumors. No cases showed loss of ATRX/DAXX expression by immunohistochemistry. TERT promoter mutations showed a lower prevalence in our series and appeared to be associated with aggressive behavior. In PTCs, telomerase activation by TERT promoter mutation might be more important than alternative lengthening of telomeres.
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