scholarly journals TERT promoter mutation is an objective clinical marker for disease progression in chondrosarcoma

2021 ◽  
Author(s):  
Yifan Zhang ◽  
Yi Chen ◽  
Chen Yang ◽  
Nelly Seger ◽  
Asle C. Hesla ◽  
...  
Keyword(s):  
Prognostic Significance ◽  
Tumor Grade ◽  
Promoter Mutation ◽  
Primary Tumors ◽  
Mutation Status ◽  
Free Survival ◽  
Metastatic Lesions ◽  
Mutational Status ◽  
Future Potential ◽  
Promoter Mutations

AbstractChondrosarcomas are the second most common malignant bone tumor. Activating promoter mutations in telomerase reverse transcriptase (TERT) was recently described by us and others as a frequent mutation in high-grade chondrosarcoma. In this study, we investigate the prognostic significance of TERT promoter mutations in 241 chondrosarcomas from 190 patients collected over 24 years (1994–2017). The TERT promoter was sequenced after microdissection of 135 chondrosarcomas from 106 patients in addition to data from our previous cohort. The TERT promoter mutation at −124 C > T was found in 45% of all patients and was significantly associated (p > 0,001) with higher tumor grade, shorter metastasis-free survival, and disease-specific survival. Additionally, TERT promoter-mutated tumors were associated with a more aggressive metastatic pattern. Shorter survival was observed in patients with wild-type primary tumors who developed a mutated metastasis indicative of tumor progression. Primary tumor genetic heterogeneity and altering mutational status between nonsynchronous metastatic lesions suggests that chondrosarcoma is a multiclonal disease progressing through a branching evolution. Conclusion: TERT promoter mutation seems to be a central event in chondrosarcoma progression with association to metastatic disease and disease-related mortality. As an easily analyzed marker, there is future potential to utilize TERT promoter mutation status as a prognostic marker and investigate telomerase-targeted therapy in chondrosarcomas.

scholarly journals Synchronous supratentorial and infratentorial oligodendrogliomas with incongruous IDH1 mutations, a case report

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Alexander H. C. W. Agopyan-Miu ◽  
Matei A. Banu ◽  
Michael L. Miller ◽  
Christopher Troy ◽  
Gunnar Hargus ◽  
...  
Keyword(s):  
Case Report ◽  
Treatment Resistance ◽  
Complete Response ◽  
Cortical Lesion ◽  
Precentral Gyrus ◽  
Primary Tumors ◽  
Metastatic Lesions ◽  
Pontine Lesion ◽  
Grade 3 ◽  
Promoter Mutations

AbstractInfratentorial oligodendrogliomas, a rare pathological entity, are generally considered metastatic lesions from supratentorial primary tumors. Here, we report the case of a 23-year-old man presenting with a histopathologically confirmed right precentral gyrus grade 2 oligodendroglioma and a concurrent pontine grade 3 oligodendroglioma. The pontine lesion was biopsied approximately a year after the biopsy of the precentral lesion due to disease progression despite 4 cycles of procarbazine-CCNU-vincristine (PCV) chemotherapy and stable supratentorial disease. Histology and genetic analysis of the pontine biopsy were consistent with grade 3 oligodendroglioma, and comparison of the two lesions demonstrated common 1p/19q co-deletions and TERT promoter mutations but distinct IDH1 mutations, with a non-canonical IDH1 R132G mutation identified in the infratentorial lesion and a R132H mutation identified in the cortical lesion. Initiation of Temozolomide led to complete response of the supratentorial lesion and durable disease control, while Temozolomide with subsequent radiation therapy of 54 Gy in 30 fractions resulted in partial response of the pontine lesion. This case report supports possible distinct molecular pathogenesis in supratentorial and infratentorial oligodendrogliomas and raises questions about the role of different IDH1 mutant isoforms in explaining treatment resistance to different chemotherapy regimens. Importantly, this case suggests that biopsies of all radiographic lesions, when feasible and safe, should be considered in order to adequately guide management in multicentric oligodendrogliomas.

scholarly journals Concordance of Acquired Mutations between Metastatic Lesions and Liquid Biopsy in Metastatic Colorectal Cancer Treated with Anti-EGFR Therapy

2021 ◽  
Author(s):  
Fumitaka Taniguchi ◽  
Akihiro Nyuya ◽  
Toshiaki Toshima ◽  
Kazuya Yasui ◽  
Yoshiko Mori ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Liquid Biopsy ◽  
Acquired Resistance ◽  
Metastatic Tumor ◽  
Primary Tumors ◽  
Blood Samples ◽  
Activating Mutations ◽  
Metastatic Lesions ◽  
Mutational Status

Abstract Background: Acquired mutations are detected in plasma. However, still few reports examine the concordance between liquid biopsy and metastatic lesions with acquired resistance. Herein we evaluated whether a polymerase chain reaction-reverse sequence-specific oligonucleotide (PCR-rSSO) method can examine the concordance between liquid biopsy and metastatic lesions with acquired resistance.Methods: Firstly, we examined the presence of acquired mutations in 7 chemoresistant metastatic lesions and blood samples obtained from a metastatic colorectal cancer (mCRC) patient without RAS activating mutations treated with anti-EGFR treatment. The patient (patient 1) displayed initial early tumor shrinkage and finally progressed to disease (PD). Blood samples were collected before the development of PD and after acquiring resistance. Next, we evaluated RAS and BRAF mutational status among blood samples, primary tumors, and metastatic lesions obtained from three additional mCRC patients without RAS activating mutations. Acquired mutations were examined using Sanger sequencing and the PCR-rSSO approach.Results: Of patient 1, metastatic tumor specimens harbored diverse acquired mutations in the KRAS gene in all of the 7 (100%) metastases, and the three acquired mutations were detected in blood specimens collected after acquiring resistance. Next, we analyzed primary tumors, metastatic lesions after chemotherapy, and blood samples from three additional mCRC patients but noted that none of the patients exhibited mutations in liquid biopsy except for one case with BRAF V600E mutation, which was confirmed in both primary tumor and peritoneal dissemination. Of the four cases, acquired mutations of RAS, as well as BRAF V600E mutation, was detected in the blood obtained only after confirmation of acquiring resistance by radiological examinations.Conclusions: Our results suggest liquid biopsy based on the PCR-rSSO is a successful procedure for capturing acquired mutations with precise information of mutational spectrum that may lend us to reach selective target agents for RAS mutations.

Characteristics of long- versus short-surviving patients (Pts): An analysis of the ARIES Observational Cohort Study (OCS) of bevacizumab (BV)-treated pts with metastatic colorectal cancer (mCRC).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 702-702
Author(s):  
Mark Kozloff ◽  
Axel Grothey ◽  
Johanna C. Bendell ◽  
Allen Lee Cohn ◽  
Tanios S. Bekaii-Saab ◽  
...  
Keyword(s):  
Performance Status ◽  
Progression Free Survival ◽  
Treatment Patterns ◽  
Primary Tumors ◽  
Mutation Status ◽  
Free Survival ◽  
Disease Characteristics ◽  
Kaplan Meier ◽  
Observational Cohort

702 Background: Median overall survival (OS) in mCRC has significantly improved over the past 20 yrs, but the observed range of OS in pts remains wide; a large percentage of pts have OS <1 yr or >4 yrs. ARIES was a prospective OCS conducted from 2006–2012 that evaluated outcomes in pts receiving BV + chemotherapy (CT) for mCRC in general clinical practice. The objective of this analysis is to examine clinical characteristics of pts with long vs short OS. Methods: This analysis included 1,417/1,550 first-line (1L) BV-treated mCRC pts who died or had complete follow-up on study. Long OS was defined as OS within the upper quartile of the analysis population (range 42–67 mos); short OS was defined as OS within the lower quartile (range 0.3–12 mos). Progression-free survival (PFS) was estimated using Kaplan-Meier methods. Pt and disease characteristics and treatment patterns were described using summary statistics. Results: Pt and disease characteristics are shown in the Table. Median PFS was 22.3 mos (95% CI, 19.9–23.3) vs. 4.9 mos (95% CI, 4.6–5.4), in the long-OS vs. short-OS groups. More pts with long OS received any second-line (2L) therapy (71% vs. 46%), and were exposed to 5-fluorouracil, oxaliplatin, and irinotecan throughout the course of their disease (53% vs. 32%) compared with pts with short OS. KRAS/BRAF mutation status was not collected. Conclusions: Pts with long OS had better baseline performance status, primary tumors more likely to have been resected, and were more likely to have received 2L CT. Additional analyses of detailed treatment patterns and safety are ongoing. Clinical trial information: NCT00388206. [Table: see text]

Prognostic significance of amplifications of stemness genes in primary luminal breast cancer depending on the response to neoadjuvant chemotherapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14655-e14655
Author(s):  
Polina Kazantseva ◽  
Elena Slonimskaya ◽  
Nicolay Litviakov ◽  
Matvey Tsyganov ◽  
Marina Ibragimova
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Median Survival ◽  
Tumor Tissue ◽  
Prognostic Significance ◽  
Complete Regression ◽  
Primary Tumors ◽  
Free Survival ◽  
Group 2 ◽  
Group 1

e14655 Background: Neoadjuvant chemotherapy (NAС) is one of the treatment options for breast cancer (BC). However, chemotherapy is known can cause intratumoral changes that increase the risk of metastasis. We have previously found that the appearance of new amplifications in the chromosomal regions harboring stemness genes (3q, 5p, 6p, 7q, 8q, 9p, 9q, 10p, 10q21.1, 13q, 16p, 18Chr, 19p) is associated with the development of hematogenous metastases in 100% of cases. In our study, we evaluated the prognostic significance of amplifications stemness genes in primary BC depending on the NAC response. Methods: The study included 104 patients with stage II-III luminal B (Her2Neu -) breast cancer. All patients received 4-8 courses of NAС followed by surgery and hormone therapy. The follow-up period was 4-10 years. Amplifications in primary tumor DNA were determined using Affymetrix high density microarrays. Metastasis-free survival was estimated using the Kaplan-Meier method. Results: Zero or only 1 amplification was identified in tumor tissue of 42 patients (41%) (group 1). Two or more amplifications were identified in tumor tissue of 60 patients (59%) (group 2). We evaluated metastasis-free survival separately in each group, depending on the NAС response. It was found that in group 1, the median survival time was 122 months in cases with partial or complete regression (PR + pCR, and 63 months in cases with stable disease or disease progression (S + P), p > 0.05. In group 2, the median survival of patients with PR + pCR was not reached, and it was 63 months in patients with S + P, p = 0.025. Conclusions: Achievement of partial or complete regression in breast cancer patients, whose primary tumors displayed 2 or more amplifications of stemness genes, was associated with the increased rates of metastasis-free survival and can be considered as a positive prognostic criterion. However, the response to NAC did not impact survival of patients with 0-1 amplification of stemness genes.

Differential Prognostic Impact Of Peripheral Blood Blast Clearance In AML Based On Type Of Therapy and FLT3 Mutation Status

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2584-2584
Author(s):  
Christopher B. Benton ◽  
Lisa Gu ◽  
Hagop M. Kantarjian ◽  
Peng Qiu ◽  
Farhad Ravandi ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Specific Treatment ◽  
Rank Test ◽  
P Value ◽  
Prognostic Impact ◽  
Mutation Status ◽  
Mutational Status

Abstract Background The day of clearance of peripheral blood blast cells (PBBC) is a prognostic marker in patients with acute myeloid leukemia (AML) treated with induction chemotherapy with cytarabine (ara-C) plus idarubicin (AI regimen: ara-C 1.5g/m2 x 4 days, idarubicin 12mg/m2 x 3 days). Earlier PBBC clearance correlates with improved overall survival (OS). We extended this observation to subsets of patients receiving the AI regimen in combination with a targeted agent such as the FLT3 inhibitor sorafenib (AI regimen plus sorafenib 400mg orally twice daily x 7 days) and vorinostat (vorinostat 500mg three times daily x 3 days followed by AI regimen), and examined the interaction of FLT3 mutational status and PBBC clearance. Patients and Methods PBBC clearance (defined as PBBC=0% by CBC differential) was examined for patients with non-APL AML undergoing AI alone (n=168), AI+sorafenib (n=75), and AI+vorinostat (n=102). Patient characteristics for all patients (n=345) were as follows: median age 54 years (range, 18-72), FLT3-mutated (FLT3+, includes FLT3-ITD and FLT3-D385) (95, 28%), wild-type FLT3 (FLT3-neg) (207, 60%), median WBC 5.0x109/dL (range, 0-229), median PBBC 17% (range, 0-99), median BM blasts 46% (range, 1-98). Patients for each cohort were divided based on day of PBBC clearance and survival evaluated by Kaplan-Meier curves. Comparisons of curves were carried out using a log-rank test. Results The overall response rates (ORR=CR+CRp) for the AI, AI+sorafenib, and AI+vorinostat induction cohorts were 63%, 79%, and 76% respectively. We evaluated OS for each of the three cohorts individually. In our first analysis, we divided patients into 5 groups according to PBBC clearance day: group A (0-1 days), B (2-3 days), C (4-5 days), D (6-8 days), and E (>8 days). We found that OS for patients in groups A-E was significantly different only in the AI therapy cohort (p-value<0.01), and not in the AI+sorafenib (p-value=0.15) or AI+vorinostat (p-value=0.1) cohorts. Noting that earlier blast clearance generally correlated with improved OS, we simplified our analysis by dividing patients into only two groups based on blast clearance. We performed two separate analyses using a 3-day cutoff (0-3 days vs. >3 days) or a 5-day cutoff (0-5 days vs. >5 days). For a blast clearance cutoff of 3 days, OS was significantly different in the AI+vorinostat cohort (p-value=0.02) and not in the AI alone (p-value=0.27) or AI+sorafenib (p-value=0.1) cohorts. For a 5-day cutoff, OS was significantly different in the AI (p-value<0.001) and AI+vorinostat (p-value=0.04) cohorts, but not the AI+sorafenib (p-value=0.13) cohort. We next evaluated FLT3+ and FLT3-neg patients individually for all three cohorts. Using a 3-day cutoff for blast clearance, the prognosis of FLT3+ patients could be significantly differentiated for patients treated with the FLT3 targeted regimen AI+sorafenib (p-value=0.04), but not AI alone (p-value=0.64) or AI+vorinostat (p-value=0.48). In distinction, FLT3-neg patients receiving AI+vorinostat could be well differentiated (p-value=0.06), but not FLT3-neg patients receiving AI alone (p-value=0.21) or AI+sorafenib (p-value=0.6). Conclusions The prognostic significance of the day of PBBC clearance during induction chemotherapy in AML is dependent on the specific treatment used and the mutation status of the patients being treated. For patients treated with AI alone, disappearance of blasts within 5 days of induction strongly predicts superior survival compared to patients who clear blasts after 5 days. For patients treated with AI+sorafenib, there is not a strong correlation between day of blast clearance and prognosis, unless FLT3+ patients are investigated alone, where there is a significant correlation between clearing blasts within 3 days of induction and prognosis. For patients treated with AI+vorinostat, disappearance of blasts within 3 days suggests a better survival in FLT3-neg but not FLT3+ patients. Additional approaches are needed to evaluate the prognostic value of clearance of PBBC in AML in the context of targeted therapy and mutational status of disease. Disclosures: No relevant conflicts of interest to declare.

Retrospective cohort study on the safety and efficacy of bevacizumab for metastatic colorectal cancer patients: The HGCSG0801 study—Efficacy of KRAS mutational status.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 680-680 ◽  
Author(s):  
Susumu Sogabe ◽  
Satoshi Yuki ◽  
Hideyuki Hayashi ◽  
Hirohito Naruse ◽  
Michio Nakamura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Kras Mutation ◽  
Statistical Tests ◽  
Progression Free Survival ◽  
Wild Type ◽  
Mutation Status ◽  
Free Survival ◽  
Mutational Status ◽  
Kras Mutation Status

680 Background: Mutations of the KRAS gene were identified as a prognostic marker in metastatic colorectal cancer(mCRC). Previously reported data suggests that the longer overall survival (OS) observed with bevacizumab(BV) treatment in mCRC is independent of alterations in the KRAS mutation status. So we analyzed efficacy of bevacizumab combined chemotherapy in mCRC relative to KRAS mutation status. Methods: In the retrospective analysis(n=212) of patients treated with BV(HGCSG0801), additional statistical analyses were done with data from KRAS mutation analyses. The Response Evaluation in Solid Tumors (RECIST) criteria version 1.0 was used to assess tumor response. The Kaplan–Meier method was used to determine Progression-free survival(PFS) and OS. Log-rank test was used to compare with mutant or wild-type KRAS in terms of PFS and OS. All statistical tests were performed using SPSS. Results: KRAS status was assessed in 88 patients (41.5%). Response rate was 58.9% with wild-type and 62.5% with mutant KRAS, that was not significant(p=0.823). The median Progression-free survival was 11.5 months with wild-type and 11.5 months with mutant KRAS, that was not significant(p=0.222). And median OS was 31.8 months with wild-type and 27.5 months with mutant KRAS, that was not significant(p=0.760) as well. Similar results were seen among patients with first-line therapy. Conclusions: Bevacizumab provides clinical benefit in patients with mCRC expressing either mutant or wild-type KRAS.

scholarly journals Prognostic Value of Circulating KRAS2 Gene Mutations in Colorectal Cancer with Distant Metastases

2006 ◽  
Vol 21 (4) ◽  
pp. 223-228 ◽  
Author(s):  
C. Trevisiol ◽  
F. Di Fabio ◽  
R. Nascimbeni ◽  
L. Peloso ◽  
C. Salbe ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Carcinoma ◽  
Residual Disease ◽  
Prognostic Significance ◽  
Primary Treatment ◽  
Tissue Samples ◽  
Primary Tumors ◽  
Mutational Status ◽  
Stage D ◽  
Related Survival

While tissue KRAS2 mutations have been extensively investigated, the role of circulating mutant KRAS2 gene in patients with colorectal carcinoma remains obscure. The aim of the present study was to explore the prognostic significance of circulating KRAS2 gene mutational status in subjects undergoing primary treatment for colorectal cancer. Codon 12 KRAS2 mutations were examined in DNA samples extracted from the serum of 86 patients with colorectal cancer and were compared with the KRAS2 status of their primary tumors. Tissue and serum KRAS2 status was compared with other clinicopathological variables (including CEA and CA 19-9 levels) and with cancer-related survival. KRAS2 mutations were found in tissue samples of 28 patients (33%); serum KRAS2 mutations were detected in 10 of them (36%). Serum KRAS2 status was significantly associated with Dukes' stage D (p=0.001) and with preoperative CA 19-9 levels (p=0.01). At multivariate analysis, cancer-related survival was associated with Dukes' stage (p<0.0001), CEA level (p=0.02), and mutant circulating KRAS2 (p=0.01). All 7 stage D patients with serum KRAS2 mutations died of the disease within 24 months of primary treatment; cancer-related survival was significantly better in 9 stage D patients without serum KRAS2 mutations, with 5 patients (56%) alive after 24 months and 1 patient (13%) alive after 44 months. Residual disease after surgery was evident in all 7 stage D patients with mutant circulating KRAS2, and in 5 out of 9 stage D patients without serum mutations. Serum KRAS2 status may impact substantially on the management of stage D colorectal carcinoma, since it appears to correlate with prognosis in this patient subgroup.

scholarly journals Prognostic significance of FLT3-ITD length in AML patients treated with intensive regimens

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tamara Castaño-Bonilla ◽  
Juan M. Alonso-Dominguez ◽  
Eva Barragán ◽  
Rebeca Rodríguez-Veiga ◽  
Claudia Sargas ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Insertion Site ◽  
Prognostic Significance ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Allelic Ratio ◽  
Mutational Status

AbstractFLT3-ITD mutations are detected in approximately 25% of newly diagnosed adult acute myeloid leukemia (AML) patients and confer an adverse prognosis. The FLT3-ITD allelic ratio has clear prognostic value. Nevertheless, there are numerous manuscripts with contradictory results regarding the prognostic relevance of the length and insertion site (IS) of the FLT3-ITD fragment. We aimed to assess the prognostic impact of these variables on the complete remission (CR) rates, overall survival (OS) and relapse-free survival (RFS) of AML patients with FLT3-ITDmutations. We studied the FLT3-ITD length of 362 adult AML patients included in the PETHEMA AML registry. We tried to validate the thresholds of ITD length previously published (i.e., 39 bp and 70 bp) in intensively treated AML patients (n = 161). We also analyzed the mutational profile of 118 FLT3-ITD AML patients with an NGS panel of 39 genes and correlated mutational status with the length and IS of ITD. The AUC of the ROC curve of the ITD length for OS prediction was 0.504, and no differences were found when applying any of the thresholds for OS, RFS or CR rate. Only four out of 106 patients had ITD IS in the TKD1 domain. Our results, alongside previous publications, confirm that FLT3-ITD length lacks prognostic value and clinical applicability.

scholarly journals Caspase-3 and Survivin Expression in Primary Atypical and Malignant Meningiomas

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Andrej Vranic
Keyword(s):  
Caspase 3 ◽  
Prognostic Significance ◽  
Survivin Expression ◽  
Tumor Grade ◽  
Proliferation Index ◽  
Free Survival ◽  
Apoptotic Marker ◽  
Meningioma Recurrence ◽  
The Difference ◽  
Atypical Meningiomas

Objective. Information about possible prognostic factors of the survival of patients with atypical and malignant meningiomas (AMM) is sparse. The aim of our study was to evaluate prognostic significance of apoptotic marker caspase-3 and apoptotic inhibitor survivin in a series of primary AMM. Methods. 86 AMM (76 atypical and 10 malignant) were analyzed. Caspase-3 and survivin expression was evaluated immunohistochemically. The correlation between caspase-3, survivin, and other possible factors of meningioma recurrence was evaluated. Uni- and multivariate recurrence-free survival (RFS) and overall survival (OS) analyses were performed. Results. The intensity of caspase-3 expression correlated with the tumor grade (P=0.004), the proliferation index (P=0.019), and the mitotic count (P=0.013). Survivin tended to be more expressed in female patients (P=0.072). Survivin expression was stronger in malignant compared to atypical meningiomas, however, the difference was not statistically important (P=0.491). Neither survivin nor caspase-3 expression significantly predicted OS or RFS in patients with AMM. Conclusions. Strong caspase-3 expression on AMM cells could reflect a cellular attempt at the homeostatic autoregulation of the tumor size. Survivin expression on AMM cells is similar to the survivin expression reported on benign meningiomas. Caspase-3 and survivin expression has no prognostic significance on the survival of patients with AMM.

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.

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