scholarly journals PLEKHS1 Over-Expression is Associated with Metastases and Poor Outcomes in Papillary Thyroid Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2133
Author(s):  
Xiangling Xing ◽  
Ninni Mu ◽  
Xiaotian Yuan ◽  
Na Wang ◽  
C. Christofer Juhlin ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Disease Free Survival ◽  
Distant Metastases ◽  
Pleckstrin Homology Domain ◽  
Gene Methylation ◽  
Akt Phosphorylation ◽  
Over Expression ◽  
Tert Promoter Mutations ◽  
Poor Outcomes ◽  
Promoter Mutations

Pleckstrin homology domain containing S1 (PLEKHS1) is a poorly characterized factor, although its promoter mutations were identified in human malignancies including thyroid carcinoma (TC). This study was designed to determine PLEKHS1 promoter hotspot mutations in papillary and anaplastic thyroid carcinomas (PTCs and ATCs) and to evaluate if PLEKHS1 expression influences clinical outcome. The PLEKHS1 promoter mutation was observed in 1/93 of PTCs and none of 18 ATCs in our cohort; however, PLEKHS1 expression was aberrantly up-regulated in TCs compared to adjacent non-tumorous thyroid tissues. ATC tumors, an undifferentiated TC, exhibited the highest PLEKHS1 expression. In both TCGA and present cohorts of PTCs, PLEKHS1 gene methylation density was inversely correlated with its mRNA expression and demethylation at the PLEKHS1 locus occurred at two CpGs. Higher PLEKHS1 expression was associated with lymph node and distant metastases, and shorter overall and disease-free survival in our cohort of PTC patients. Importantly, PLEKHS1 over-expression predicted shorter patient survival in PTCs lacking TERT promoter mutations. Cellular experiments showed that PLEKHS1 over-expression enhanced AKT phosphorylation and invasiveness. Collectively, the PLEKHS1 gene demethylation causes its over-expression in PTCs. PLEKHS1 promotes aggressive behavior of TCs possibly by increasing AKT activity, and its over-expression predicts poor patient outcomes.

scholarly journals TERT Immunohistochemistry Is a Poor Predictor of TERT Promoter Mutations and Gene Expression in Follicular Thyroid Carcinoma

2018 ◽  
Vol 29 (4) ◽  
pp. 380-383 ◽  
Author(s):  
Johan O. Paulsson ◽  
Anton Olander ◽  
Felix Haglund ◽  
Jan Zedenius ◽  
C. Christofer Juhlin
Keyword(s):  
Gene Expression ◽  
Thyroid Carcinoma ◽  
Follicular Thyroid Carcinoma ◽  
Poor Predictor ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

scholarly journals TERT promoter mutations are associated with distant metastases in papillary thyroid carcinoma

2015 ◽  
Vol 172 (4) ◽  
pp. 403-413 ◽  
Author(s):  
Greta Gandolfi ◽  
Moira Ragazzi ◽  
Andrea Frasoldati ◽  
Simonetta Piana ◽  
Alessia Ciarrocchi ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Direct Sequencing ◽  
Distant Metastases ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Mutational Status ◽  
Metastatic Behavior ◽  
Well Differentiated ◽  
Promoter Mutations

ObjectiveTranscriptional activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene were reported at high frequency in aggressive poorly differentiated and anaplastic thyroid cancers. By contrast, the relevance of these mutations in the metastatic behavior of well-differentiated thyroid cancer is still to be defined. The aim of this work was to investigate the frequency ofTERTpromoter mutations in a remarkable cohort of well-differentiated papillary thyroid carcinoma that developed distant metastases (DM-PTCs) and to establish whether these mutations may be predictive of metastatic behavior.DesignWe analyzed the frequency ofTERTpromoter mutations in a group of 43 highly aggressive DM-PTCs. As controls, we analyzed these mutations in a group of 78 PTCs without distant metastases (control-PTCs). The possible correlation betweenTERTpromoter mutations and BRAF V600E mutation was also investigated.MethodsTERTpromoter mutational status was evaluated by direct sequencing of the hotspot harboring the C228T and the C250T mutations.ResultsIn the overall cohort of 121 PTCs analyzed, 17% of cases (21/121) carried a mutation in theTERTpromoter. Noticeably, 33% of DM-PTCs were mutated in theTERTpromoter while only 9% of the control-PTCs showed a mutation in this locus. We also observed a positive association between BRAF V600E andTERTC228T mutations in the cohort of DM-PTCs.ConclusionsThese results indicate thatTERTpromoter mutations are associated with the development of distant metastases in PTCs and may help in predicting aggressive behavior in this type of tumor.

scholarly journals Radioactive iodine in the treatment of medullary thyroid carcinoma: a controlled multicenter study

2013 ◽  
Vol 168 (5) ◽  
pp. 779-786 ◽  
Author(s):  
J A A Meijer ◽  
L E H Bakker ◽  
G D Valk ◽  
W W de Herder ◽  
J H W de Wilt ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Multicenter Study ◽  
Radioactive Iodine ◽  
Disease Free Survival ◽  
Distant Metastases ◽  
Medullary Thyroid ◽  
Clinical Appearance ◽  
Significant Difference

ObjectiveRadioactive iodine (RAI) therapy in medullary thyroid carcinoma (MTC) is applied in some centers, based on the assumption that cross-irradiation from thyroid follicular cells may be beneficial. However, no systematic studies on the effect of RAI treatment in MTC have been performed. The aim of this study was to analyze the effect of RAI treatment on survival in MTC patients.DesignRetrospective multicenter study in eight University Medical Centers in The Netherlands.MethodsTwo hundred and ninety three MTC patients without distant metastases who had undergone a total thyroidectomy were included between 1980 and 2007. Patients were stratified by clinical appearance, hereditary stage, screening status, and localization. All patients underwent regular surgical treatment with additional RAI treatment in 61 patients. Main outcome measures were disease-free survival (DFS) and disease-specific survival (DSS). Cure was defined as biochemical and radiological absence of disease.ResultsIn multivariate analysis, stratification according to clinical appearance (P=0.72), hereditary stage (P=0.96), localization (P=0.69), and screening status (P=0.31) revealed no significant effects of RAI treatment on DFS. Multivariate analysis showed no significant difference in DSS for the two groups stratified according to clinical appearance (P=0.14). Owing to limited number of events, multivariate analysis was not possible for DSS in the other groups of stratification.ConclusionsBased on the results of the present analysis, we conclude that RAI has no place in the treatment of MTC.

BRAFV600E and TERT promoter mutations in paediatric and young adult papillary thyroid cancer and clinicopathological correlation

2020 ◽  
Vol 33 (11) ◽  
pp. 1465-1474
Author(s):  
Dhritiman Chakraborty ◽  
Sunil Shakya ◽  
Sanjana Ballal ◽  
Shipra Agarwal ◽  
Chandrasekhar Bal
Keyword(s):  
Thyroid Cancer ◽  
Young Adult ◽  
Univariate Analysis ◽  
Distant Metastases ◽  
Primary Objective ◽  
Papillary Thyroid ◽  
Promoter Mutation ◽  
Tert Promoter Mutations ◽  
Secondary Objective ◽  
Promoter Mutations

AbstractObjectivesThe primary objective of this study was to determine the prevalence of BRAFV600E and TERTpromoter mutations in paediatric and young adult patients with papillary thyroid carcinoma (PTC) and the secondary objective, to assess their association with clinicopathological features.MethodsPatients ≤20 years who underwent surgery for differentiated thyroid cancer (DTC) from 2005 to 2018 were consecutively enrolled for BRAFV600E and TERTpromoter mutations analysis and records analysed for the association of aggressive features. Univariate analysis and multivariate logistic regression were used to identify the independent predictors of BRAFV600E mutations.ResultsAmong 100 patients with DTC, 68 patients were ≤18 years and the remaining 30 patients were >18 years of age with a median age of 17 years (IQR 14–19 years) 98 patients had PTC and 2 had FTC. BRAFV600E mutation was present in 14/98 (14.3%) PTC and TERTpromoter mutation noted in none. Multivariate analysis identified RAI refractoriness (OR:10.57, 95% CI: 2.6 to 41.6, P-0.0008) as an independent factor associated with BRAFV600E mutation. 17 patients with distant metastases were negative for both BRAFV600E or TERTpromoter mutation. No significant association was observed between age, gender, PTC variants, extra-thyroidal extension, lymphovascular invasion, multifocality, RAI administration and event rate with BRAFV600E mutation. Irrespective of BRAFV600E mutation, radioiodine refractory status (p-0.0001) had a reduced EFS probability.ConclusionIn paediatric & young adult PTC, TERTpromoter mutation is absent and BRAFV600E mutation is not associated with distant metastasis. The prevalence rate of the BRAFV600E mutation is much lower compared to adult PTC patients.

scholarly journals BRAF and TERT promoter mutations in the aggressiveness of papillary thyroid carcinoma: a study of 653 patients

Oncotarget ◽  
2016 ◽  
Vol 7 (14) ◽  
pp. 18346-18355 ◽  
Author(s):  
Langping Jin ◽  
Endong Chen ◽  
Siyang Dong ◽  
Yefeng Cai ◽  
Xiangjian Zhang ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Papillary Thyroid ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

scholarly journals Low Prevalence of Somatic TERT Promoter Mutations in Classic Papillary Thyroid Carcinoma

2016 ◽  
Vol 31 (1) ◽  
pp. 100 ◽  
Author(s):  
Min Ji Jeon ◽  
Won Gu Kim ◽  
Soyoung Sim ◽  
Seonhee Lim ◽  
Hyemi Kwon ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Papillary Thyroid ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Low Prevalence ◽  
Promoter Mutations

scholarly journals BRAF V600E and TERT Promoter Mutations in Papillary Thyroid Carcinoma in Chinese Patients

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0153319 ◽  
Author(s):  
Jian Sun ◽  
Jing Zhang ◽  
Junliang Lu ◽  
Jie Gao ◽  
Xinyu Ren ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Braf V600e ◽  
Chinese Patients ◽  
Papillary Thyroid ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

Disease-free survival in papillary and follicular thyroid carcinoma

2013 ◽  
Vol 52 (03) ◽  
pp. 71-80 ◽  
Author(s):  
M. Meixner ◽  
M. Hellmich ◽  
M. Dietlein ◽  
C. Kobe ◽  
H. Schicha ◽  
...  
Keyword(s):  
Lymph Node ◽  
Thyroid Carcinoma ◽  
Cervical Lymph Node ◽  
Tumour Size ◽  
Primary Tumour ◽  
Disease Free Survival ◽  
Distant Metastases ◽  
Free Survival ◽  
Explained Variation ◽  
Disease Free

SummaryT stage was redefined for patients with differentiated thyroid carcinoma (DTC) between the 5th and 7th versions of the UICC tumour classification system. Patients, methods: 636 patients (486 women, 150 men; mean age 49.1 ± 15.6 years, mean follow-up 4.6 years) who had been treated with ablative radioiodine therapy after thyroidectomy for papillary (PTC) or follicular thyroid carcinomas (FTC) were retrospectively assessed on occurrence of locoregional recurrent disease, or cervical lymph node or distant metastases. Disease-free survival was calculated from initial T stage, classified according to both versions of the UICC staging system and compared with the prognostic value of primary tumour size. Kaplan-Meier method and two measures of explained variation, (1) R2 based on the (partial) likelihood ratio statistic of the Cox proportional hazards model and (2) a model-free variant of a distance measure proposed by Schemper had the aim to detect the most advantageous classification. Results: Of the 508 patients with PTC, 11 (2.2%) developed a local recurrence, 37 (7.3%) cervical lymph node and 23 (4.5%) distant metastases, 3 (2.3%), 8 (6.3%), and 18 (14.1%) were the numbers for the 128 FTC patients respectively. The two classification systems yielded an equal count of statistically significant differences regarding disease-free survival in patients with PTC while UICC 7th classification appeared slightly advantageous in patients with FTC. Regarding explained variation the UICC 7th classification tended to be superior to the UICC 5th classification, both in PTC and FTC, however statistical significance was not reached. Conclusion: The primary tumour size significantly added to the prognosis regarding local cervical and distant metastases.

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