scholarly journals Proposal of a New Prognostic Model for Differentiated Thyroid Cancer with TERT Promoter Mutations

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2943
Author(s):  
Jun Park ◽  
Sungjoo Lee ◽  
Jiyun Park ◽  
Hyunju Park ◽  
Chang-Seok Ki ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Cox Regression ◽  
Term Survival ◽  
Poor Prognostic Factor ◽  
Prognostic System ◽  
Tert Promoter ◽  
Mutational Status ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

The role of telomerase reverse transcriptase (TERT) promoter mutations as an independent poor prognostic factor in differentiated thyroid cancer (DTC) patients is well known, but there is no prognostic system that combines the TERT promoter mutation status with tumor-node-metastasis (TNM) stage to predict cancer-specific survival (CSS). A total of 393 patients with pathologically confirmed DTC after thyroidectomy were enrolled. After incorporating wild-type TERT and mutant TERT with stages I, II, and III/IV of the AJCC TNM system 8th edition (TNM-8), we generated six combinations and calculated 10-year and 15-year CSS and adjusted hazard ratios (HRs) for cancer-related death using Cox regression. Then, a new mortality prediction model termed TNM-8T was derived based on the CSS and HR of each combination in the four groups. Of the 393 patients, there were 27 (6.9%) thyroid cancer-related deaths during a median follow-up of 14 years. Patients with a more advanced stage had a lower survival rate (10-year CSS for TNM-8T stage 1, 2, 3, and 4: 98.7%, 93.5%, 77.3%, and 63.0%, respectively; p < 0.001). TNM-8T showed a better spread of CSS (p < 0.001) than TNM-8 (p = 0.002) in the adjusted survival curves. The C-index for mortality risk predictability was 0.880 (95% CI, 0.665–0.957) in TNM-8T and 0.827 (95% CI, 0.622–0.930) in TNM-8 (p < 0.001). TNM-8T, a new prognostic system that incorporates the TERT mutational status into TNM-8, showed superior predictability to TNM-8 in the long-term survival of DTC patients.

scholarly journals Refining Dynamic Risk Stratification and Prognostic Groups for Differentiated Thyroid Cancer With TERT Promoter Mutations

2017 ◽  
Vol 102 (5) ◽  
pp. 1757-1764 ◽  
Author(s):  
Tae Hyuk Kim ◽  
Chang-Seok Ki ◽  
Hye Seung Kim ◽  
Kyunga Kim ◽  
Jun-Ho Choe ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Risk Stratification ◽  
Differentiated Thyroid Cancer ◽  
Cox Regression ◽  
Molecular Testing ◽  
Prognostic System ◽  
Dynamic Risk ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

Abstract Context: Currently, no recurrence or mortality risk systems consider molecular testing when predicting thyroid cancer outcomes. Objective: We developed an integrative prognostic system that incorporates telomerase reverse transcription (TERT) promoter mutations into the recently proposed risk reclassification system after initial therapy [dynamic risk stratification (DRS)] to better categorize and predict outcomes. Design: A total of 357 differentiated thyroid cancer (DTC) patients without initial distant metastasis were enrolled. Among patients with mutated TERT and wild-type, recurrence-free survival (RFS) was compared according to DRS grouping. Cox regression was used to calculate adjusted hazard ratios (AHRs) to derive AHR groups. Performance of the AHR grouping system with respect to prediction of structural recurrence and cancer-specific survival (CSS) was assessed against the current DRS system and the tumor/node/metastasis (TNM) classification. Results: Among 357 patients, there were 90 recurrences and 15 cancer-related deaths during a median of 14 years of follow-up. Patients in higher AHR groups were at higher risk of recurrence (10-year RFS for AHR 1, 2, 3, and 4: 94.9%, 82.7%, 50.2%, and 23.1%; P &lt; 0.001) and cancer-related death (10-year CSS: 100.0%. 98.7%, 94.2%, and 76.9%; P &lt; 0.001). The proportions of variance explained (PVEs) for the ability of AHR and DRS grouping to predict recurrence were 22.4% and 18.5%. PVEs of AHR and TNM system to predict cancer-related deaths were 11.5% and 7.4%. Conclusions: The AHR grouping system, a simple two-dimensional prognostic system, is as effective as DRS at predicting structural recurrence and provides clinical implication for long-term CSS in patients with nonmetastatic DTC.

scholarly journals Aggressive differentiated thyroid cancer with multiple metastases and NRAS and TERT promoter mutations: A case report

2017 ◽  
Vol 14 (2) ◽  
pp. 2186-2190
Author(s):  
Fabiana Pani ◽  
Elisabetta Macerola ◽  
Fulvio Basolo ◽  
Francesco Boi ◽  
Mario Scartozzi ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Case Report ◽  
Differentiated Thyroid Cancer ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Multiple Metastases ◽  
Promoter Mutations

scholarly journals TERT promoter mutations and long-term survival in patients with thyroid cancer

2016 ◽  
Vol 23 (10) ◽  
pp. 813-823 ◽  
Author(s):  
Tae Hyuk Kim ◽  
Young-Eun Kim ◽  
Soomin Ahn ◽  
Ji-Youn Kim ◽  
Chang-Seok Ki ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Survival Rate ◽  
Cancer Patients ◽  
Differentiated Thyroid Cancer ◽  
Promoter Mutation ◽  
Papillary Cancer ◽  
Term Survival ◽  
Extrathyroidal Invasion ◽  
Mutational Status ◽  
Promoter Mutations

TERT promoter mutations are emerging prognostic biomarkers in multiple cancers and are found in highly aggressive thyroid cancer. Our aim is to investigate the prognostic value of these mutations for the outcome of thyroid cancer-related mortality in a large cohort of thyroid cancer patients. This was a retrospective study of 409 patients (393 with differentiated thyroid cancer) with a median age of 44 years (range 16–81 years) and median follow-up of 13 years (interquartile range 11–16 years). Analyses of associations between mutational status and various clinicopathological variables were performed. TERT promoter mutations were identified in 32 (9.8%) papillary, 11 (16.7%) follicular and seven (43.8%) poorly differentiated/anaplastic thyroid cancer patients. The presence of TERT promoter mutations was associated with factors such as increased age (P < 0.001), extrathyroidal invasion (P = 0.01), increased stage at diagnosis (P < 0.001) and dedifferentiated histological type (P = 0.001). A TERT promoter mutation was independently associated with poorer overall survival in patients with differentiated thyroid cancer (10-year survival rate, 66.2% vs 98.3% for wild type; adjusted HR, 7.18; 95% CI: 2.77–18.59) and in patients with papillary cancer (74.2% vs 99.3%; 14.20; 3.03–66.68). Concomitant TERT and BRAF mutations worsened the survival rate of patients with papillary cancer (82.6% vs 99.4% for exclusively BRAF mutation alone; 5.62; 1.85–17.09). In conclusion, the presence of TERT promoter mutations is independently associated with increased mortality in patients with differentiated thyroid cancer. The results suggest that inclusion of TERT promoter mutation analysis with conventional clinicopathological evaluation can lead to better prognostication and management for individual patients.

In papillary thyroid cancer TERT promoter mutations have a worst impact on outcome than BRAF mutations

2015 ◽  
Author(s):  
Marina Muzza ◽  
Carla Colombo ◽  
Maria Carla Proverbio ◽  
Stefania Rossi ◽  
Delfina Tosi ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Papillary Thyroid ◽  
Braf Mutations ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

scholarly journals TERT Promoter Mutations and the 8th Edition TNM Classification in Predicting the Survival of Thyroid Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 648
Author(s):  
Jun Park ◽  
Sungjoo Lee ◽  
Kyunga Kim ◽  
Hyunju Park ◽  
Chang-Seok Ki ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Prognostic Factor ◽  
Histologic Type ◽  
Stage At Diagnosis ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Specific Mortality ◽  
Cancer Specific Mortality ◽  
Promoter Mutations ◽  
8Th Edition

Our research group has previously shown that the presence of TERT promoter mutations is an independent prognostic factor, by applying the TERT mutation status to the variables of the AJCC 7th edition. This study aimed to determine if TERT mutations could be independent predictors of thyroid cancer-specific mortality based on the AJCC TNM 8th edition, with long-term follow-up. This was a retrospective study of 393 patients with pathologically confirmed differentiated thyroid carcinoma (DTC) after thyroidectomy at a tertiary Korean hospital from 1994 to 2004. The thyroid cancer-specific mortality rate was 6.9% (5.2% for papillary and 15.2% for follicular cancers). TERT promoter mutations were identified in 10.9% (43/393) of DTC cases (9.8% of papillary and 16.7% of follicular cancer) and were associated with older age (p < 0.001), the presence of extrathyroidal invasion (p < 0.001), distant metastasis (p = 0.001), and advanced stage at diagnosis (p < 0.001). The 10-year survival rate in mutant TERT was 67.4% for DTC patients (vs. 98% for wild-type; adjusted hazard ratio (HR) of 9.93, (95% CI: 3.67–26.90)) and 75% for patients with papillary cancer (vs. 99%; 18.55 (4.83–71.18)). In addition, TERT promoter mutations were related to poor prognosis regardless of histologic type (p < 0.001 for both papillary and follicular cancer) or initial stage (p < 0.001, p = 0.004, and p = 0.086 for stages I, II, and III and IV, respectively). TERT promoter mutations comprise an independent poor prognostic factor after adjusting for the clinicopathological risk factors of the AJCC TNM 8th edition, histologic type, and each stage at diagnosis, which could increase prognostic predictability for patients with DTC.

scholarly journals TERT promoter mutations in thyroid cancer: growing evidence for a predictor of poor outcome

Gland Surgery ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 301-303 ◽  
Author(s):  
Jianliang Man ◽  
Norman Nicolson ◽  
Courtney Gibson ◽  
Tobias Carling
Keyword(s):  
Thyroid Cancer ◽  
Poor Outcome ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

scholarly journals TERT Promoter Mutations are Associated with Visceral Spreading in Melanoma of the Trunk

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 452 ◽  
Author(s):  
Simona Osella-Abate ◽  
Luca Bertero ◽  
Rebecca Senetta ◽  
Sara Mariani ◽  
Francesco Lisa ◽  
...  
Keyword(s):  
Logistic Regression ◽  
External Validation ◽  
Multivariate Logistic Regression Analysis ◽  
Primary Melanoma ◽  
Control Group ◽  
Tert Promoter ◽  
Mutational Status ◽  
Tert Promoter Mutations ◽  
Melanoma Patients ◽  
Promoter Mutations

Survival predictions are currently determined on the basis of NRAS/BRAF mutations, even though TERT promoter mutations have been recently associated with a poor prognosis in stage I-II melanomas. Usually, it is not recommended to perform a mutational test on primary melanoma, as the results do not always reflect the mutational status of metastases. In particular, trunk melanomas have been reported to have an unfavourable prognosis. A series of 105 advanced melanoma patients were analysed by TERT promoter Sanger sequencing. Univariate/multivariate binary logistic regression models were performed using progression to a visceral site as the dependent variable and patient/tumour characteristics as covariates. Performance of the model was assessed in an external independent primary melanoma patients’ dataset. Male gender (odds ratio (OR), 344; 95% CI, 1.12–10.6; p = 0.031), AJCC (American Joint Committee on Cancer) classification (OR, 022; 95% CI, 0.07–0.67; p = 0.008), SLNB (Sentinel Lymph Node Biopsy) status (OR, 3.05; 95% CI, 1.06–8.78; p = 0.039) and TERT-mutated trunk lesions (OR, 3.78; 95% CI, 1.35–10.6; p =  0.011) were significantly associated with the risk of developing a visceral spreading as first site of progression using multivariate logistic regression analysis. These results were confirmed in the external validation control group. Therefore, in trunk primary melanomas, due to their high risk of progression to visceral sites, we encourage somatic TERT mutation analysis at diagnosis to identify those patients who would potentially benefit from a more intensive follow-up protocol and a prompt initiation of therapy.

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