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...

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Published in:Endocrine-related cancer Vol. 22; no. 3; pp. 419 - 429
Main Authors: Dettmer, Matthias S, Schmitt, Anja, Steinert, Hans, Capper, David, Moch, Holger, Komminoth, Paul, Perren, Aurel
Format: Journal Article
Language:English
Published: England 01.06.2015
Subjects:
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
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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
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  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
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  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
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BRAF
TERT
papillary thyroid carcinoma
prognosis
tall cell
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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...
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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
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