TERT promoter mutations identify a high-risk group in metastasis-free advanced thyroid carcinoma
TERT promoter mutations are associated with adverse clinicopathological characteristics in thyroid carcinomas and considered as a major indicator of poor outcomes. Nevertheless, most studies have pooled heterogeneous types of thyroid carcinomas and have been conducted retrospectively. We investigate...
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| Veröffentlicht in: | European journal of cancer (1990) 2019-02, Vol.108, p.41-49 |
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| creator | Bournaud, Claire Descotes, Françoise Decaussin-Petrucci, Myriam Berthiller, Julien de la Fouchardière, Christelle Giraudet, Anne-Laure Bertholon-Gregoire, Mireille Robinson, Philip Lifante, Jean-Christophe Lopez, Jonathan Borson-Chazot, Françoise |
| description | TERT promoter mutations are associated with adverse clinicopathological characteristics in thyroid carcinomas and considered as a major indicator of poor outcomes. Nevertheless, most studies have pooled heterogeneous types of thyroid carcinomas and have been conducted retrospectively. We investigated the association between TERT promoter mutations and recurrence in a prospective series of 173 intermediate- to high-risk patients with thyroid cancer.
Patients referred for radioiodine treatment after thyroidectomy for intermediate- to high-risk differentiated thyroid carcinoma were included in a prospective observational study and tested for TERT promoter, BRAF, and RAS mutations of their primary tumours. We analysed the relationship between TERT promoter mutations and outcomes.
The prevalence of TERT promoter mutations was 20.2% (35/173) in the total population. It was significantly higher in tumours harbouring aggressive histological features (poorly differentiated carcinoma, tall cell variant of papillary cancer or widely invasive follicular cancer) than in non-aggressive tumours: 32.7% (16/49) versus 15.3% (19/124; p = 0.020). TERT promoter mutations were also strongly associated with age ≥45 years (p = 0.005), pT4 stage (p = 0.015), metastatic disease (p = 0.014), and extrathyroidal extension (p = 0.002). TERT promoter mutations were associated with poor outcomes in the total population (p |
| doi_str_mv | 10.1016/j.ejca.2018.12.003 |
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Patients referred for radioiodine treatment after thyroidectomy for intermediate- to high-risk differentiated thyroid carcinoma were included in a prospective observational study and tested for TERT promoter, BRAF, and RAS mutations of their primary tumours. We analysed the relationship between TERT promoter mutations and outcomes.
The prevalence of TERT promoter mutations was 20.2% (35/173) in the total population. It was significantly higher in tumours harbouring aggressive histological features (poorly differentiated carcinoma, tall cell variant of papillary cancer or widely invasive follicular cancer) than in non-aggressive tumours: 32.7% (16/49) versus 15.3% (19/124; p = 0.020). TERT promoter mutations were also strongly associated with age ≥45 years (p = 0.005), pT4 stage (p = 0.015), metastatic disease (p = 0.014), and extrathyroidal extension (p = 0.002). TERT promoter mutations were associated with poor outcomes in the total population (p < 0.001) but not in the subgroup of non-metastatic patients (p = 0.051). However, they were associated with a worse outcome in patients both free of metastases and devoid of aggressive histological features. Neither BRAF nor RAS mutations were associated with event-free survival in non-metastatic patients.
Although their prognostic value does not seem to overcome that of histology, TERT promoter mutations may help to better define the prognosis of localized thyroid cancer patients without aggressive histology.
•TERT mutations are associated with clinicopathological adverse features, even in intermediate- to high-risk thyroid cancer.•In intermediate- to high-risk thyroid cancer, TERT mutations do not overcome the prognostic value of histological features.•TERT mutations may be useful to identify high-risk patients among those without adverse histological features.</description><identifier>ISSN: 0959-8049</identifier><identifier>EISSN: 1879-0852</identifier><identifier>DOI: 10.1016/j.ejca.2018.12.003</identifier><identifier>PMID: 30648628</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adenocarcinoma, Follicular - genetics ; Adenocarcinoma, Follicular - pathology ; Adenocarcinoma, Follicular - therapy ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cancer ; Female ; GTP Phosphohydrolases - genetics ; Health risks ; Histology ; Humans ; Invasiveness ; Iodine 131 ; Iodine radioisotopes ; Iodine Radioisotopes - therapeutic use ; Kaplan-Meier Estimate ; Life Sciences ; Male ; Medical prognosis ; Membrane Proteins - genetics ; Metastases ; Metastasis ; Middle Aged ; Mutation ; Neoplasm Metastasis ; Patients ; Prognosis ; Prognostic factors ; Promoter Regions, Genetic - genetics ; Proportional Hazards Models ; Proto-Oncogene Proteins B-raf - genetics ; Proto-Oncogene Proteins p21(ras) - genetics ; Radiotherapy, Adjuvant ; Risk ; Risk groups ; Subgroups ; Telomerase - genetics ; TERT promoter mutations ; Thyroid ; Thyroid cancer ; Thyroid Cancer, Papillary - genetics ; Thyroid Cancer, Papillary - pathology ; Thyroid Cancer, Papillary - therapy ; Thyroid carcinoma ; Thyroid Neoplasms - genetics ; Thyroid Neoplasms - pathology ; Thyroid Neoplasms - therapy ; Thyroidectomy ; Tumors ; Young Adult</subject><ispartof>European journal of cancer (1990), 2019-02, Vol.108, p.41-49</ispartof><rights>2019 Elsevier Ltd</rights><rights>Copyright © 2019 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Science Ltd. Feb 2019</rights><rights>Attribution - NonCommercial</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c462t-34f37766f98aadcd4bfd653a76db8a95210a751b83d1a0934de2de33823072013</citedby><cites>FETCH-LOGICAL-c462t-34f37766f98aadcd4bfd653a76db8a95210a751b83d1a0934de2de33823072013</cites><orcidid>0000-0003-2515-7840 ; 0000-0003-3768-2378 ; 0000-0003-2291-5693</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejca.2018.12.003$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,315,782,786,887,3554,27933,27934,46004</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30648628$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-03486174$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Bournaud, Claire</creatorcontrib><creatorcontrib>Descotes, Françoise</creatorcontrib><creatorcontrib>Decaussin-Petrucci, Myriam</creatorcontrib><creatorcontrib>Berthiller, Julien</creatorcontrib><creatorcontrib>de la Fouchardière, Christelle</creatorcontrib><creatorcontrib>Giraudet, Anne-Laure</creatorcontrib><creatorcontrib>Bertholon-Gregoire, Mireille</creatorcontrib><creatorcontrib>Robinson, Philip</creatorcontrib><creatorcontrib>Lifante, Jean-Christophe</creatorcontrib><creatorcontrib>Lopez, Jonathan</creatorcontrib><creatorcontrib>Borson-Chazot, Françoise</creatorcontrib><title>TERT promoter mutations identify a high-risk group in metastasis-free advanced thyroid carcinoma</title><title>European journal of cancer (1990)</title><addtitle>Eur J Cancer</addtitle><description>TERT promoter mutations are associated with adverse clinicopathological characteristics in thyroid carcinomas and considered as a major indicator of poor outcomes. Nevertheless, most studies have pooled heterogeneous types of thyroid carcinomas and have been conducted retrospectively. We investigated the association between TERT promoter mutations and recurrence in a prospective series of 173 intermediate- to high-risk patients with thyroid cancer.
Patients referred for radioiodine treatment after thyroidectomy for intermediate- to high-risk differentiated thyroid carcinoma were included in a prospective observational study and tested for TERT promoter, BRAF, and RAS mutations of their primary tumours. We analysed the relationship between TERT promoter mutations and outcomes.
The prevalence of TERT promoter mutations was 20.2% (35/173) in the total population. It was significantly higher in tumours harbouring aggressive histological features (poorly differentiated carcinoma, tall cell variant of papillary cancer or widely invasive follicular cancer) than in non-aggressive tumours: 32.7% (16/49) versus 15.3% (19/124; p = 0.020). TERT promoter mutations were also strongly associated with age ≥45 years (p = 0.005), pT4 stage (p = 0.015), metastatic disease (p = 0.014), and extrathyroidal extension (p = 0.002). TERT promoter mutations were associated with poor outcomes in the total population (p < 0.001) but not in the subgroup of non-metastatic patients (p = 0.051). However, they were associated with a worse outcome in patients both free of metastases and devoid of aggressive histological features. Neither BRAF nor RAS mutations were associated with event-free survival in non-metastatic patients.
Although their prognostic value does not seem to overcome that of histology, TERT promoter mutations may help to better define the prognosis of localized thyroid cancer patients without aggressive histology.
•TERT mutations are associated with clinicopathological adverse features, even in intermediate- to high-risk thyroid cancer.•In intermediate- to high-risk thyroid cancer, TERT mutations do not overcome the prognostic value of histological features.•TERT mutations may be useful to identify high-risk patients among those without adverse histological features.</description><subject>Adenocarcinoma, Follicular - genetics</subject><subject>Adenocarcinoma, Follicular - pathology</subject><subject>Adenocarcinoma, Follicular - therapy</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Cancer</subject><subject>Female</subject><subject>GTP Phosphohydrolases - genetics</subject><subject>Health risks</subject><subject>Histology</subject><subject>Humans</subject><subject>Invasiveness</subject><subject>Iodine 131</subject><subject>Iodine radioisotopes</subject><subject>Iodine Radioisotopes - therapeutic use</subject><subject>Kaplan-Meier Estimate</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Membrane Proteins - genetics</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Neoplasm Metastasis</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Prognostic factors</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Proportional Hazards Models</subject><subject>Proto-Oncogene Proteins B-raf - genetics</subject><subject>Proto-Oncogene Proteins p21(ras) - genetics</subject><subject>Radiotherapy, Adjuvant</subject><subject>Risk</subject><subject>Risk groups</subject><subject>Subgroups</subject><subject>Telomerase - genetics</subject><subject>TERT promoter mutations</subject><subject>Thyroid</subject><subject>Thyroid cancer</subject><subject>Thyroid Cancer, Papillary - genetics</subject><subject>Thyroid Cancer, Papillary - pathology</subject><subject>Thyroid Cancer, Papillary - therapy</subject><subject>Thyroid carcinoma</subject><subject>Thyroid Neoplasms - genetics</subject><subject>Thyroid Neoplasms - pathology</subject><subject>Thyroid Neoplasms - therapy</subject><subject>Thyroidectomy</subject><subject>Tumors</subject><subject>Young Adult</subject><issn>0959-8049</issn><issn>1879-0852</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kV9rFDEUxYModlv9Aj5IwJf2Ycb8m0kCvpRSrbAgyPocs8mdbsadyZrMLOy3N8PWPvggBC6E3z3ccw5C7yipKaHtx76G3tmaEapqympC-Au0okrqiqiGvUQrohtdKSL0BbrMuSeESCXIa3TBSStUy9QK_dzcf9_gQ4pDnCDhYZ7sFOKYcfAwTqE7YYt34XFXpZB_4ccU5wMOIx5gsrm8kKsuAWDrj3Z04PG0O6UYPHY2uTDGwb5Brzq7z_D2aV6hH5_vN3cP1frbl693t-vKiZZNFRcdl7JtO62s9c6LbefbhlvZ-q2yumGUWNnQreKeWqK58MA8cK4YJ7IkwK_QzVl3Z_fmkMJg08lEG8zD7dosf4QXy1SK48Jen9ni-_cMeTJDyA72eztCnLNhVGqupGhEQT_8g_ZxTmNxUiitGWeMqUKxM-VSzDlB93wBJWbpyvRm6cosXRnKTOmqLL1_kp63A_jnlb_lFODTGYCS2zFAMtkFWGIOCdxkfAz_0_8DuPOjsg</recordid><startdate>20190201</startdate><enddate>20190201</enddate><creator>Bournaud, Claire</creator><creator>Descotes, Françoise</creator><creator>Decaussin-Petrucci, Myriam</creator><creator>Berthiller, Julien</creator><creator>de la Fouchardière, Christelle</creator><creator>Giraudet, Anne-Laure</creator><creator>Bertholon-Gregoire, Mireille</creator><creator>Robinson, Philip</creator><creator>Lifante, Jean-Christophe</creator><creator>Lopez, Jonathan</creator><creator>Borson-Chazot, Françoise</creator><general>Elsevier Ltd</general><general>Elsevier Science Ltd</general><general>Elsevier</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><orcidid>https://orcid.org/0000-0003-2515-7840</orcidid><orcidid>https://orcid.org/0000-0003-3768-2378</orcidid><orcidid>https://orcid.org/0000-0003-2291-5693</orcidid></search><sort><creationdate>20190201</creationdate><title>TERT promoter mutations identify a high-risk group in metastasis-free advanced thyroid carcinoma</title><author>Bournaud, Claire ; Descotes, Françoise ; Decaussin-Petrucci, Myriam ; Berthiller, Julien ; de la Fouchardière, Christelle ; Giraudet, Anne-Laure ; Bertholon-Gregoire, Mireille ; Robinson, Philip ; Lifante, Jean-Christophe ; Lopez, Jonathan ; Borson-Chazot, Françoise</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c462t-34f37766f98aadcd4bfd653a76db8a95210a751b83d1a0934de2de33823072013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adenocarcinoma, Follicular - genetics</topic><topic>Adenocarcinoma, Follicular - pathology</topic><topic>Adenocarcinoma, Follicular - therapy</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Cancer</topic><topic>Female</topic><topic>GTP Phosphohydrolases - genetics</topic><topic>Health risks</topic><topic>Histology</topic><topic>Humans</topic><topic>Invasiveness</topic><topic>Iodine 131</topic><topic>Iodine radioisotopes</topic><topic>Iodine Radioisotopes - therapeutic use</topic><topic>Kaplan-Meier Estimate</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Membrane Proteins - genetics</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Neoplasm Metastasis</topic><topic>Patients</topic><topic>Prognosis</topic><topic>Prognostic factors</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Proportional Hazards Models</topic><topic>Proto-Oncogene Proteins B-raf - genetics</topic><topic>Proto-Oncogene Proteins p21(ras) - genetics</topic><topic>Radiotherapy, Adjuvant</topic><topic>Risk</topic><topic>Risk groups</topic><topic>Subgroups</topic><topic>Telomerase - genetics</topic><topic>TERT promoter mutations</topic><topic>Thyroid</topic><topic>Thyroid cancer</topic><topic>Thyroid Cancer, Papillary - genetics</topic><topic>Thyroid Cancer, Papillary - pathology</topic><topic>Thyroid Cancer, Papillary - therapy</topic><topic>Thyroid carcinoma</topic><topic>Thyroid Neoplasms - genetics</topic><topic>Thyroid Neoplasms - pathology</topic><topic>Thyroid Neoplasms - therapy</topic><topic>Thyroidectomy</topic><topic>Tumors</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bournaud, Claire</creatorcontrib><creatorcontrib>Descotes, Françoise</creatorcontrib><creatorcontrib>Decaussin-Petrucci, Myriam</creatorcontrib><creatorcontrib>Berthiller, Julien</creatorcontrib><creatorcontrib>de la Fouchardière, Christelle</creatorcontrib><creatorcontrib>Giraudet, Anne-Laure</creatorcontrib><creatorcontrib>Bertholon-Gregoire, Mireille</creatorcontrib><creatorcontrib>Robinson, Philip</creatorcontrib><creatorcontrib>Lifante, Jean-Christophe</creatorcontrib><creatorcontrib>Lopez, Jonathan</creatorcontrib><creatorcontrib>Borson-Chazot, Françoise</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>European journal of cancer (1990)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bournaud, Claire</au><au>Descotes, Françoise</au><au>Decaussin-Petrucci, Myriam</au><au>Berthiller, Julien</au><au>de la Fouchardière, Christelle</au><au>Giraudet, Anne-Laure</au><au>Bertholon-Gregoire, Mireille</au><au>Robinson, Philip</au><au>Lifante, Jean-Christophe</au><au>Lopez, Jonathan</au><au>Borson-Chazot, Françoise</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TERT promoter mutations identify a high-risk group in metastasis-free advanced thyroid carcinoma</atitle><jtitle>European journal of cancer (1990)</jtitle><addtitle>Eur J Cancer</addtitle><date>2019-02-01</date><risdate>2019</risdate><volume>108</volume><spage>41</spage><epage>49</epage><pages>41-49</pages><issn>0959-8049</issn><eissn>1879-0852</eissn><abstract>TERT promoter mutations are associated with adverse clinicopathological characteristics in thyroid carcinomas and considered as a major indicator of poor outcomes. Nevertheless, most studies have pooled heterogeneous types of thyroid carcinomas and have been conducted retrospectively. We investigated the association between TERT promoter mutations and recurrence in a prospective series of 173 intermediate- to high-risk patients with thyroid cancer.
Patients referred for radioiodine treatment after thyroidectomy for intermediate- to high-risk differentiated thyroid carcinoma were included in a prospective observational study and tested for TERT promoter, BRAF, and RAS mutations of their primary tumours. We analysed the relationship between TERT promoter mutations and outcomes.
The prevalence of TERT promoter mutations was 20.2% (35/173) in the total population. It was significantly higher in tumours harbouring aggressive histological features (poorly differentiated carcinoma, tall cell variant of papillary cancer or widely invasive follicular cancer) than in non-aggressive tumours: 32.7% (16/49) versus 15.3% (19/124; p = 0.020). TERT promoter mutations were also strongly associated with age ≥45 years (p = 0.005), pT4 stage (p = 0.015), metastatic disease (p = 0.014), and extrathyroidal extension (p = 0.002). TERT promoter mutations were associated with poor outcomes in the total population (p < 0.001) but not in the subgroup of non-metastatic patients (p = 0.051). However, they were associated with a worse outcome in patients both free of metastases and devoid of aggressive histological features. Neither BRAF nor RAS mutations were associated with event-free survival in non-metastatic patients.
Although their prognostic value does not seem to overcome that of histology, TERT promoter mutations may help to better define the prognosis of localized thyroid cancer patients without aggressive histology.
•TERT mutations are associated with clinicopathological adverse features, even in intermediate- to high-risk thyroid cancer.•In intermediate- to high-risk thyroid cancer, TERT mutations do not overcome the prognostic value of histological features.•TERT mutations may be useful to identify high-risk patients among those without adverse histological features.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>30648628</pmid><doi>10.1016/j.ejca.2018.12.003</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-2515-7840</orcidid><orcidid>https://orcid.org/0000-0003-3768-2378</orcidid><orcidid>https://orcid.org/0000-0003-2291-5693</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | European journal of cancer (1990), 2019-02, Vol.108, p.41-49 |
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| language | eng |
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| subjects | Adenocarcinoma, Follicular - genetics Adenocarcinoma, Follicular - pathology Adenocarcinoma, Follicular - therapy Adolescent Adult Aged Aged, 80 and over Cancer Female GTP Phosphohydrolases - genetics Health risks Histology Humans Invasiveness Iodine 131 Iodine radioisotopes Iodine Radioisotopes - therapeutic use Kaplan-Meier Estimate Life Sciences Male Medical prognosis Membrane Proteins - genetics Metastases Metastasis Middle Aged Mutation Neoplasm Metastasis Patients Prognosis Prognostic factors Promoter Regions, Genetic - genetics Proportional Hazards Models Proto-Oncogene Proteins B-raf - genetics Proto-Oncogene Proteins p21(ras) - genetics Radiotherapy, Adjuvant Risk Risk groups Subgroups Telomerase - genetics TERT promoter mutations Thyroid Thyroid cancer Thyroid Cancer, Papillary - genetics Thyroid Cancer, Papillary - pathology Thyroid Cancer, Papillary - therapy Thyroid carcinoma Thyroid Neoplasms - genetics Thyroid Neoplasms - pathology Thyroid Neoplasms - therapy Thyroidectomy Tumors Young Adult |
| title | TERT promoter mutations identify a high-risk group in metastasis-free advanced thyroid carcinoma |
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