Tall cell papillary thyroid carcinoma: new diagnostic criteria and mutations in BRAF and TERT

The tall cell (TC) variant of papillary thyroid carcinoma (PTC) has an unfavorable prognosis. The diagnostic criteria remain inconsistent, and the role of a minor TC component is unclear. Molecular diagnostic markers are not available; however, there are two potential candidates: BRAF V600E and telo...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Endocrine-related cancer Jg. 22; H. 3; S. 419 - 429
Hauptverfasser: Dettmer, Matthias S, Schmitt, Anja, Steinert, Hans, Capper, David, Moch, Holger, Komminoth, Paul, Perren, Aurel
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England 01.06.2015
Schlagworte:
Carcinoma - enzymology
Carcinoma - genetics
Carcinoma - pathology
Carcinoma, Papillary
Female
Humans
Male
Middle Aged
Mutation
Prognosis
Proto-Oncogene Proteins B-raf - genetics
Telomerase - genetics
Thyroid Cancer, Papillary
Thyroid Neoplasms - enzymology
Thyroid Neoplasms - genetics
Thyroid Neoplasms - pathology
Treatment Outcome
diagnostic criteria
BRAF
TERT
papillary thyroid carcinoma
prognosis
tall cell
ISSN:1479-6821
Online-Zugang:Weitere Angaben
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Abstract The tall cell (TC) variant of papillary thyroid carcinoma (PTC) has an unfavorable prognosis. The diagnostic criteria remain inconsistent, and the role of a minor TC component is unclear. Molecular diagnostic markers are not available; however, there are two potential candidates: BRAF V600E and telomerase reverse transcriptase (TERT) promoter mutations. Using a novel approach, we enriched a collective with PTCs that harbored an adverse outcome, which overcame the limited statistical power of most studies. This enabled us to review 125 PTC patients, 57 of which had an adverse outcome. The proportion of TCs that constituted a poor prognosis was assessed. All of the tumors underwent sequencing for TERT promoter and BRAF V600E mutational status and were stained with an antibody to detect the BRAF V600E mutation. A 10% cutoff for TCs was significantly associated with advanced tumor stage and lymph node metastasis. Multivariate analysis showed that TCs above 10% were the only significant factor for overall, tumor-specific, and relapse-free survival. Seven percent of the cases had a TERT promoter mutation, whereas 61% demonstrated a BRAF mutation. The presence of TC was significantly associated with TERT promoter and BRAF mutations. TERT predicted highly significant tumor relapse (P<0.001). PTCs comprised of at least 10% TCs are associated with an adverse clinical outcome and should be reported accordingly. BRAF did not influence patient outcome. Nevertheless, a positive status should encourage the search for TCs. TERT promoter mutations are a strong predictor of tumor relapse, but their role as a surrogate marker for TCs is limited.
AbstractList The tall cell (TC) variant of papillary thyroid carcinoma (PTC) has an unfavorable prognosis. The diagnostic criteria remain inconsistent, and the role of a minor TC component is unclear. Molecular diagnostic markers are not available; however, there are two potential candidates: BRAF V600E and telomerase reverse transcriptase (TERT) promoter mutations. Using a novel approach, we enriched a collective with PTCs that harbored an adverse outcome, which overcame the limited statistical power of most studies. This enabled us to review 125 PTC patients, 57 of which had an adverse outcome. The proportion of TCs that constituted a poor prognosis was assessed. All of the tumors underwent sequencing for TERT promoter and BRAF V600E mutational status and were stained with an antibody to detect the BRAF V600E mutation. A 10% cutoff for TCs was significantly associated with advanced tumor stage and lymph node metastasis. Multivariate analysis showed that TCs above 10% were the only significant factor for overall, tumor-specific, and relapse-free survival. Seven percent of the cases had a TERT promoter mutation, whereas 61% demonstrated a BRAF mutation. The presence of TC was significantly associated with TERT promoter and BRAF mutations. TERT predicted highly significant tumor relapse (P<0.001). PTCs comprised of at least 10% TCs are associated with an adverse clinical outcome and should be reported accordingly. BRAF did not influence patient outcome. Nevertheless, a positive status should encourage the search for TCs. TERT promoter mutations are a strong predictor of tumor relapse, but their role as a surrogate marker for TCs is limited.
Author Komminoth, Paul
Schmitt, Anja
Dettmer, Matthias S
Moch, Holger
Steinert, Hans
Capper, David
Perren, Aurel
Author_xml – sequence: 1
  givenname: Matthias S
  surname: Dettmer
  fullname: Dettmer, Matthias S
  email: dettmerms@gmail.com, matthias.dettmer@pathology.unibe.ch
  organization: Institute of PathologyUniversity of Bern, Murtenstrasse 31, 3010 Bern, SwitzerlandDivision of Nuclear MedicineUniversity Hospital Zurich, Zurich, SwitzerlandDepartment of NeuropathologyInstitute of Pathology, German Cancer Research Center (DKFZ), Ruprecht-Karls University, and Clinical Cooperation Unit Neuropathology, Heidelberg, GermanyInstitute of Surgical PathologyUniversity Hospital Zurich, Zurich, SwitzerlandInstitute of Surgical PathologyTriemlispital, Zürich, Switzerland dettmerms@gmail.com matthias.dettmer@pathology.unibe.ch
– sequence: 2
  givenname: Anja
  surname: Schmitt
  fullname: Schmitt, Anja
  organization: Institute of PathologyUniversity of Bern, Murtenstrasse 31, 3010 Bern, SwitzerlandDivision of Nuclear MedicineUniversity Hospital Zurich, Zurich, SwitzerlandDepartment of NeuropathologyInstitute of Pathology, German Cancer Research Center (DKFZ), Ruprecht-Karls University, and Clinical Cooperation Unit Neuropathology, Heidelberg, GermanyInstitute of Surgical PathologyUniversity Hospital Zurich, Zurich, SwitzerlandInstitute of Surgical PathologyTriemlispital, Zürich, Switzerland
– sequence: 3
  givenname: Hans
  surname: Steinert
  fullname: Steinert, Hans
  organization: Institute of PathologyUniversity of Bern, Murtenstrasse 31, 3010 Bern, SwitzerlandDivision of Nuclear MedicineUniversity Hospital Zurich, Zurich, SwitzerlandDepartment of NeuropathologyInstitute of Pathology, German Cancer Research Center (DKFZ), Ruprecht-Karls University, and Clinical Cooperation Unit Neuropathology, Heidelberg, GermanyInstitute of Surgical PathologyUniversity Hospital Zurich, Zurich, SwitzerlandInstitute of Surgical PathologyTriemlispital, Zürich, Switzerland
– sequence: 4
  givenname: David
  surname: Capper
  fullname: Capper, David
  organization: Institute of PathologyUniversity of Bern, Murtenstrasse 31, 3010 Bern, SwitzerlandDivision of Nuclear MedicineUniversity Hospital Zurich, Zurich, SwitzerlandDepartment of NeuropathologyInstitute of Pathology, German Cancer Research Center (DKFZ), Ruprecht-Karls University, and Clinical Cooperation Unit Neuropathology, Heidelberg, GermanyInstitute of Surgical PathologyUniversity Hospital Zurich, Zurich, SwitzerlandInstitute of Surgical PathologyTriemlispital, Zürich, Switzerland
– sequence: 5
  givenname: Holger
  surname: Moch
  fullname: Moch, Holger
  organization: Institute of PathologyUniversity of Bern, Murtenstrasse 31, 3010 Bern, SwitzerlandDivision of Nuclear MedicineUniversity Hospital Zurich, Zurich, SwitzerlandDepartment of NeuropathologyInstitute of Pathology, German Cancer Research Center (DKFZ), Ruprecht-Karls University, and Clinical Cooperation Unit Neuropathology, Heidelberg, GermanyInstitute of Surgical PathologyUniversity Hospital Zurich, Zurich, SwitzerlandInstitute of Surgical PathologyTriemlispital, Zürich, Switzerland
– sequence: 6
  givenname: Paul
  surname: Komminoth
  fullname: Komminoth, Paul
  organization: Institute of PathologyUniversity of Bern, Murtenstrasse 31, 3010 Bern, SwitzerlandDivision of Nuclear MedicineUniversity Hospital Zurich, Zurich, SwitzerlandDepartment of NeuropathologyInstitute of Pathology, German Cancer Research Center (DKFZ), Ruprecht-Karls University, and Clinical Cooperation Unit Neuropathology, Heidelberg, GermanyInstitute of Surgical PathologyUniversity Hospital Zurich, Zurich, SwitzerlandInstitute of Surgical PathologyTriemlispital, Zürich, Switzerland
– sequence: 7
  givenname: Aurel
  surname: Perren
  fullname: Perren, Aurel
  organization: Institute of PathologyUniversity of Bern, Murtenstrasse 31, 3010 Bern, SwitzerlandDivision of Nuclear MedicineUniversity Hospital Zurich, Zurich, SwitzerlandDepartment of NeuropathologyInstitute of Pathology, German Cancer Research Center (DKFZ), Ruprecht-Karls University, and Clinical Cooperation Unit Neuropathology, Heidelberg, GermanyInstitute of Surgical PathologyUniversity Hospital Zurich, Zurich, SwitzerlandInstitute of Surgical PathologyTriemlispital, Zürich, Switzerland
BackLink https://www.ncbi.nlm.nih.gov/pubmed/25870252$$D View this record in MEDLINE/PubMed
BookMark eNo1kM9LwzAcxYMozk1P3iVHL9UkbX7U2xybCgNh1KOUb9pUI21akxTZf2_VeXkPHh8evDdHx653BqFLSm4oT8nterdKKE8I4fIIndFM5olQjM7QPIQPQohQnJ-iGeNKEsbZGXotoG1xZSYZYLBtC36P4_ve97bGFfjKur6DO-zMF64tvLk-RFvhyttovAUMrsbdGCHa3gVsHb7fLTe_abHeFefopIE2mIuDL9DLZl2sHpPt88PTarlNdCZkTKjmhlZAFQjWECmkrFOi8kaRFEzW5DCp1iknTaqkAalBG9oYlWpN8jpjbIGu_3oH33-OJsSys-FnFDjTj6GkQqWSiywTE3p1QEfdmbocvO2mzeX_Jewb0iViOQ
CitedBy_id crossref_primary_10_1016_j_pathol_2017_01_001
crossref_primary_10_1007_s12022_025_09859_y
crossref_primary_10_1158_1541_7786_MCR_16_0003
crossref_primary_10_2147_TACG_S412364
crossref_primary_10_1097_CCO_0000000000000248
crossref_primary_10_3390_genes9050241
crossref_primary_10_1016_j_mpdhp_2019_02_001
crossref_primary_10_1089_thy_2015_0488
crossref_primary_10_1093_jnen_nlw106
crossref_primary_10_1016_j_jss_2024_03_023
crossref_primary_10_3390_genes7070038
crossref_primary_10_1016_j_path_2019_07_001
crossref_primary_10_3892_ol_2017_5948
crossref_primary_10_1007_s00292_019_0600_9
crossref_primary_10_1186_s13000_016_0458_6
crossref_primary_10_1089_thy_2017_0280
crossref_primary_10_1007_s12022_018_9548_1
crossref_primary_10_1007_s40618_022_01958_5
crossref_primary_10_1016_j_prp_2025_156112
crossref_primary_10_1097_PAP_0000000000000184
crossref_primary_10_3390_cancers15072152
crossref_primary_10_1007_s12022_018_9561_4
crossref_primary_10_1097_MD_0000000000011548
crossref_primary_10_1016_j_humpath_2025_105867
crossref_primary_10_1007_s12022_023_09788_8
crossref_primary_10_1097_MED_0000000000000559
crossref_primary_10_1007_s00292_019_0613_4
crossref_primary_10_1177_1010428318787720
crossref_primary_10_1093_jscr_rjac215
crossref_primary_10_1111_pin_12737
crossref_primary_10_1371_journal_pone_0272696
crossref_primary_10_1097_PAP_0000000000000198
crossref_primary_10_3389_fendo_2022_969914
crossref_primary_10_3390_cancers11060885
crossref_primary_10_3390_genes7080050
crossref_primary_10_1007_s12020_019_02117_2
crossref_primary_10_1016_j_jpi_2024_100366
crossref_primary_10_3390_jcm13206119
crossref_primary_10_1007_s12022_023_09775_z
crossref_primary_10_1016_j_ejca_2018_12_003
crossref_primary_10_1007_s12022_016_9435_6
crossref_primary_10_1016_j_prp_2022_154012
crossref_primary_10_1245_s10434_019_07444_2
crossref_primary_10_1002_hed_27025
crossref_primary_10_1016_j_surg_2021_05_054
crossref_primary_10_3389_fmed_2022_882727
crossref_primary_10_1089_thy_2020_0668
crossref_primary_10_1530_EC_18_0333
crossref_primary_10_1053_j_semdp_2020_03_002
crossref_primary_10_1097_MD_0000000000024237
crossref_primary_10_1016_j_mrrev_2016_11_002
ContentType Journal Article
Copyright 2015 Society for Endocrinology.
Copyright_xml – notice: 2015 Society for Endocrinology.
DBID CGR
CUY
CVF
ECM
EIF
NPM
7X8
DOI 10.1530/ERC-15-0057
DatabaseName Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
MEDLINE - Academic
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
MEDLINE - Academic
DatabaseTitleList MEDLINE
MEDLINE - Academic
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: 7X8
  name: MEDLINE - Academic
  url: https://search.proquest.com/medline
  sourceTypes: Aggregation Database
DeliveryMethod no_fulltext_linktorsrc
Discipline Medicine
EISSN 1479-6821
EndPage 429
ExternalDocumentID 25870252
Genre Research Support, Non-U.S. Gov't
Journal Article
GroupedDBID ---
0R~
0VX
18M
2WC
4.4
53G
5GY
5VS
AALGN
ABOCM
ABSQV
ACGFO
ADBBV
ADDZX
ADMOG
AENEX
AFHIN
ALMA_UNASSIGNED_HOLDINGS
BAWUL
C1A
CGR
CS3
CUY
CVF
DIK
DU5
E3Z
EBS
ECM
EIF
EJD
F5P
F9R
GX1
H13
HZ~
IL9
INIJC
KQ8
NPM
O9-
OK1
P2P
REN
TBS
TR2
UDS
W8F
WOQ
7X8
ID FETCH-LOGICAL-b467t-1b5e1ca18a62f07677d3089f803ae4f9aae4bb350f387ea7babe1fe83bb09d422
IEDL.DBID 7X8
ISICitedReferencesCount 65
ISICitedReferencesURI http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000359003500023&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
IngestDate Wed Oct 01 13:44:31 EDT 2025
Mon Jul 21 06:04:27 EDT 2025
IsDoiOpenAccess false
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 3
Keywords diagnostic criteria
BRAF
TERT
papillary thyroid carcinoma
prognosis
tall cell
Language English
License 2015 Society for Endocrinology.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-b467t-1b5e1ca18a62f07677d3089f803ae4f9aae4bb350f387ea7babe1fe83bb09d422
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
OpenAccessLink https://erc.bioscientifica.com/downloadpdf/journals/erc/22/3/419.pdf
PMID 25870252
PQID 1683756446
PQPubID 23479
PageCount 11
ParticipantIDs proquest_miscellaneous_1683756446
pubmed_primary_25870252
PublicationCentury 2000
PublicationDate 2015-06-01
PublicationDateYYYYMMDD 2015-06-01
PublicationDate_xml – month: 06
  year: 2015
  text: 2015-06-01
  day: 01
PublicationDecade 2010
PublicationPlace England
PublicationPlace_xml – name: England
PublicationTitle Endocrine-related cancer
PublicationTitleAlternate Endocr Relat Cancer
PublicationYear 2015
SSID ssj0006855
Score 2.4112737
Snippet The tall cell (TC) variant of papillary thyroid carcinoma (PTC) has an unfavorable prognosis. The diagnostic criteria remain inconsistent, and the role of a...
SourceID proquest
pubmed
SourceType Aggregation Database
Index Database
StartPage 419
SubjectTerms Carcinoma - enzymology
Carcinoma - genetics
Carcinoma - pathology
Carcinoma, Papillary
Female
Humans
Male
Middle Aged
Mutation
Prognosis
Proto-Oncogene Proteins B-raf - genetics
Telomerase - genetics
Thyroid Cancer, Papillary
Thyroid Neoplasms - enzymology
Thyroid Neoplasms - genetics
Thyroid Neoplasms - pathology
Treatment Outcome
Title Tall cell papillary thyroid carcinoma: new diagnostic criteria and mutations in BRAF and TERT
URI https://www.ncbi.nlm.nih.gov/pubmed/25870252
https://www.proquest.com/docview/1683756446
Volume 22
WOSCitedRecordID wos000359003500023&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText
inHoldings 1
isFullTextHit
isPrint
link http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1La9tAEF7SJpRekvSRNk1SNtDrktU-tLu9lCTE5BAbYxzwJZh9gsGWXD8K_feZlRR8ChR62YNAQhqNvvk0MzsfQj9oNDFB5CPRO0uE9o4Y4QRRxgfNo2FFaEbmP6jBQE8mZtgl3NZdW-ULJjZAHWqfc-RXRQm_UhKid_lr-Ztk1ahcXe0kNN6gfQ5UJnu1muymhZdaym5PnuT06m50SwpJ8v7L1_lkE1d6R_97R8fosGOU-Lp1gQ9oL1Yf0bt-VzP_hJ7Gdj7HOUGPl3aZRYZWfzG8nlU9C9hnKaGqXtifGPg1Dm3jHVwJA5rkMc4W2yrgxbat2K_xrMI3o-tecxSY8PgzeuzdjW_vSSeqQBxg4oYUTsbC20LbkiWqSqUCp9okTbmNIhkLq3Nc0sS1ilY562KRoubOURMEYyfobVVX8SvCPgE_8yEKI6LgTFurRAL8oFYHyj07RZcvhpuC0-YHtVWst-vpznSn6Etr_emyna4xZRIghEn27R_OPkPvgcDItnXrHO0n-GTjBTrwfzaz9ep74w2wDob9Z-aMwdI
linkProvider ProQuest
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Tall+cell+papillary+thyroid+carcinoma%3A+new+diagnostic+criteria+and+mutations+in+BRAF+and+TERT&rft.jtitle=Endocrine-related+cancer&rft.au=Dettmer%2C+Matthias+S&rft.au=Schmitt%2C+Anja&rft.au=Steinert%2C+Hans&rft.au=Capper%2C+David&rft.date=2015-06-01&rft.eissn=1479-6821&rft.volume=22&rft.issue=3&rft.spage=419&rft_id=info:doi/10.1530%2FERC-15-0057&rft_id=info%3Apmid%2F25870252&rft_id=info%3Apmid%2F25870252&rft.externalDocID=25870252