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Tall cell Papillary Thyroid Carcinoma: new diagnostic criteria and mutations in BRAF and TERT


Dettmer, Matthias S; Schmitt, Anja Maria; Steinert, Hans; Capper, David; Moch, Holger; Komminoth, Paul; Perren, Aurel (2015). Tall cell Papillary Thyroid Carcinoma: new diagnostic criteria and mutations in BRAF and TERT. Endocrine-Related Cancer, 22(3):419-429.

Abstract

OBJECTIVE: The tall cell variant of papillary thyroid carcinoma (PTC) has an unfavorable prognosis. The diagnostic criteria remain inconsistent and the role of a minor tall cell (TC) component is unclear. Molecular diagnostic markers are not available; however, there are two potential candidates: BRAF V600E and TERT promoter mutations.
METHODS: Using a novel approach, we enriched a collective with PTC harboring an adverse outcome, overcoming the limited statistical power of most studies. This enabled us to review 125 PTC patients, 57 of them with an adverse outcome. The proportion of TC that constitute a poor prognosis was assessed. All tumors underwent sequencing for TERT promoter and BRAF V600E mutational status and were stained with an antibody detecting the BRAF V600E mutation.
RESULTS: A 10% cut off for TC was significantly associated with advanced tumor stage and lymph node metastasis. Multivariate analysis showed that tall cells above 10% were the only significant factor for overall, tumor-specific and relapse-free survival. 7% of cases had a TERT promoter mutation while 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).
CONCLUSION: PTC comprising of at least 10% TC 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 tall cells. TERT promoter mutations are a strong predictor of tumor relapse but their role as a surrogate marker for TC is limited.

Abstract

OBJECTIVE: The tall cell variant of papillary thyroid carcinoma (PTC) has an unfavorable prognosis. The diagnostic criteria remain inconsistent and the role of a minor tall cell (TC) component is unclear. Molecular diagnostic markers are not available; however, there are two potential candidates: BRAF V600E and TERT promoter mutations.
METHODS: Using a novel approach, we enriched a collective with PTC harboring an adverse outcome, overcoming the limited statistical power of most studies. This enabled us to review 125 PTC patients, 57 of them with an adverse outcome. The proportion of TC that constitute a poor prognosis was assessed. All tumors underwent sequencing for TERT promoter and BRAF V600E mutational status and were stained with an antibody detecting the BRAF V600E mutation.
RESULTS: A 10% cut off for TC was significantly associated with advanced tumor stage and lymph node metastasis. Multivariate analysis showed that tall cells above 10% were the only significant factor for overall, tumor-specific and relapse-free survival. 7% of cases had a TERT promoter mutation while 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).
CONCLUSION: PTC comprising of at least 10% TC 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 tall cells. TERT promoter mutations are a strong predictor of tumor relapse but their role as a surrogate marker for TC is limited.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Nuclear Medicine
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:13 April 2015
Deposited On:06 May 2015 09:50
Last Modified:08 Dec 2017 12:57
Publisher:European Society of Endocrinology
ISSN:1351-0088
Additional Information:Disclaimer. This is not the definitive version of record of this article. This manuscript has been accepted for publication in Endocr Relat Cancer, but the version presented here has not yet been copy edited, formatted or proofed. Consequently, the Society for Endocrinology accepts no responsibility for any errors or omissions it may contain. The definitive version is now freely available at 10.1530/ERC-15-0057 2015 Society for Endocrinology.
Publisher DOI:https://doi.org/10.1530/ERC-15-0057
PubMed ID:25870252

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