BRAF ^V600E and TERT promoter mutations in paediatric and young adult papillary thyroid cancer and clinicopathological correlation

Abstract

ObjectivesThe 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.

Predicting factors of central lymph node metastasis and BRAFV600E mutation in Chinese population with papillary thyroid carcinoma

“…Our results suggested 30 years might be a more appropriate cutoff age for predicting the risk for CLNM among Chinese patients. The results of a previous study indicated that the frequency of lymph node metastasis was 67% (64/95) in pediatric and young adult PTC patients (age ≤ 20 years) [ 17 ]. The correlation between age and CLNM needs to be further studied in a larger population.…”

Molecular Landscape of Pediatric Thyroid Cancer: A Review

“…This multivariate analysis revealed RAI refractoriness to be significantly associated with BRAF V600E mutation. However, none of the 17 patients with distant metastases had BRAF V600E mutation, and there was a lack of any significant association of BRAF V600E mutation with the status of disease recurrence or progression [ 71 ]. Contrasting results were reported by Alzahrani, who found persistent/recurrent disease to be significantly more common in patients with BRAF V600E mutation than in those without [ 7 ].…”

“…None of their pediatric patients had this alteration [ 63 ]. In a recent study from India, none of the 98 patients harbored TERT promoter mutations [ 71 ]. In another study based on 81 sporadic pediatric PTC patients from Japan, TERT promoter mutations were absent in all [ 65 ].…”

Thyroid Surgery in Children: A 5-Year Retrospective Study at a Single Paediatric Surgical Center and Systematic Review

“…The only test that can detect increased risk of malignancy is molecular testing (BRAF V600E , RET/PTC gene and NTRK–fusion) [ 7 ]. In the case of inconclusive molecular testing or if those tests are unavailable, diagnostic lobectomy is an appropriate surgical option.…”