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07.10.2016 | Original Article | Ausgabe 6/2016

Virchows Archiv 6/2016

In Japanese patients with papillary thyroid carcinoma, TERT promoter mutation is associated with poor prognosis, in contrast to BRAFV600E mutation

Zeitschrift:
Virchows Archiv > Ausgabe 6/2016
Autoren:
Almira Nasirden, Tsuyoshi Saito, Yuki Fukumura, Kieko Hara, Keisuke Akaike, Aiko Kurisaki-Arakawa, Miki Asahina, Atsushi Yamashita, Ran Tomomasa, Takuo Hayashi, Atsushi Arakawa, Takashi Yao
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s00428-016-2027-5) contains supplementary material, which is available to authorized users.

Abstract

The prognostic value of BRAFV600E and TERT promoter mutation in papillary thyroid carcinoma (PTC) is controversial. We examined alterations in BRAFV600E 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 BRAFV600E mutation was found in 53 patients (38.2 %) but was not associated with any clinicopathological factors. TERT mutations were not correlated with BRAFV600E mutation status. TERT mutation-positive tumors (TERT+) showed lower DFSR than BRAFV600E-mutation-positive tumors (BRAFV600E+), and TERT+/BRAFV600E+ tumors showed lower DFSR than BRAFV600E+ 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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