Abstract 5505: TERT promoter mutations in primary papillary thyroid carcinomas and matched local / distant metastases

TERT promoter (TERTp) mutations represent a common oncogenic event in sporadic thyroid follicular cell carcinogenesis. Though TERTp mutations have been statistically associated with aggressiveness and metastatic spreading, their involvement in lymph node metastases (LNMs) and / or distant metastases (DMs) development among papillary thyroid carcinoma (PTC) patients remains to be defined. To evaluate the role of TERTp mutations on metastatic tumor expansion, primary tumors (Pt) and matched LNMs and/or DMs were genotyped by means of PCR-direct sequencing in a cohort of 33 patients diagnosed of PTC, which had been previously analyzed for BRAF and RAS mutations. Focal changes in the growth pattern or microscopic grade within the Pt or the metastases were separately genotyped to determine the clonal/subclonal nature of TERTp mutations, their association with particular histological variants of PTC or their presence in intra-tumoral PDC-like foci. Results were correlated with clinico-pathological parameters of pour outcome and survival. The analysis of 99 tumor samples obtained from 33 PTC cases revealed that TERTp mutations were quite common (42.4%).The mutation C228T was much more common than the C250T (78,6% vs 21,4%). TERTp mutations did not correlate with specific PTC subtypes [CL-PTC, FV-PTC or Mixed-PTC] and were subclonal in half of the cases. The mutations segregated to LNMs in 73% of cases [100% CL-PTC and FV-PTC; 57% Mixed PTC]. In 2 Mixed-PTC cases the mutation seemingly originated the novo in the LNM. TERTp mutations were present in all samples of DM. While 71% of the cases mutated at TERTp bore the BRAFV600E mutation, the coexistence of TERTp and RAS mutations was exceptional. TERTp mutations were found to be significantly correlated with age ≥ 45 years old, high grade poorly differentiated PTC foci or nesting-PDC-like foci, stage at diagnosis or at last follow-up and patient status. A trend of correlation with male sex, vascular invasion, tumor recurrence and development of LNM during the follow-up was also seen. Tumor multifocality was inversely correlated with TERTp mutations. The coexistence of TERTp and BRAFV600E mutants did not increase the prognostic power of TERTp mutations alone. All of the patients who died of disease displayed TERTp mutations. Kaplan-Meier analysis revealed that patients with PTC bearing TERTp mutations had a poor prognosis showing a higher tumor recurrence probability [p= 0.0085] and a reduced disease specific survival [p Citation Format: Noa Feas Rodriguez, Miram Corraliza Gomez, Tomas Alvarez Gago, Juan Jose Mateos Otero, Raquel Munoz Martinez, Ginesa Maria Garcia-Rostan. TERT promoter mutations in primary papillary thyroid carcinomas and matched local / distant metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5505. doi:10.1158/1538-7445.AM2017-5505