title: In Japanese patients with papillary thyroid carcinoma, TERT promoter mutation is associated with poor prognosis, in contrast to BRAFV600Emutation.
abstract: The prognostic value of BRAFV600Eand TERT promoter mutation in papillary thyroid carcinoma (PTC) is controversial. We examined alterations in BRAFV600Eand 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 BRAFV600Emutation was found in 53 patients (38.2 %) but was not associated with any clinicopathological factors. TERT mutations were not correlated with BRAFV600Emutation 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.
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Almira
authors.initials: A
authors.lastname: Nasirden
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan. tysaitou@juntendo.ac.jp.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Fukumura
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Kieko
authors.initials: K
authors.lastname: Hara
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.|Department of Orthopaedic Surgery, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Akaike
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Kurisaki-Arakawa
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Asahina
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamashita
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Ran
authors.initials: R
authors.lastname: Tomomasa
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Takuo
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Arakawa
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yao
mesh_terms: D000328:Adult; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019098:Telomerase / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C509186:TERT protein, human; D019098:Telomerase
keywords: BRAF; Papillary carcinoma; TERT; Telomere maintenance; Thyroid