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. 2025 Apr 24;36(1):15.
doi: 10.1007/s12022-025-09853-4.

TERT Amplification a Risk Stratification Marker in Papillary Thyroid Carcinoma, Significantly Correlated with Tumor Recurrence and Survival

Sara Gil-Bernabé  1   2 , Noa Feás-Rodríguez  1 , Enrique Pérez-Riesgo  1   3 , Miriam Corraliza-Gómez  1   4 , Joaquín Fra Rodríguez  5 , Ginesa García-Rostán  6   7
Affiliations

TERT Amplification a Risk Stratification Marker in Papillary Thyroid Carcinoma, Significantly Correlated with Tumor Recurrence and Survival

Sara Gil-Bernabé et al. Endocr Pathol. .

Erratum in

Abstract

Few studies have analyzed the prevalence of TERT amplification in thyroid cancer, showing discrepancies in various topics. The impact on tumor recurrence and patient survival in papillary thyroid carcinoma (PTC) remains unknown. Thirteen cancer cell lines and 215 tumor samples from 91 patients, who underwent surgery for PTC (41), poorly differentiated thyroid carcinoma (PDC = 15), or anaplastic thyroid carcinoma (ATC = 35), were analyzed. Clonality, spread with tumor dedifferentiation or metastatic PTC cells, and coexistence with TERTp, BRAF, RAS, and PIK3CA mutations were also investigated. TERT amplification was found in 17%, 20%, and 17% of the PTC, PDC, and ATC, respectively. It was more frequent in follicular variant PTC and PTC with distant metastases (86%, P = 0.0448). The cell lines HTh74, SW1736, and T242 had amplification. In PTC, TERT amplification was a subclonal event. The increase in TERT copy number spread in all cases with metastatic PTC cells. In 67% of the PDC and 100% of the ATC, TERT activation segregated with tumor dedifferentiation. TERT amplification correlated with TERTp mutations in PTC (P = 0.0313) and PIK3CA mutations in ATC (P = 0.0272). TERT amplification significantly correlated with vascular invasion (P = 0.03637), distant metastases at diagnosis and/or follow-up (P = 0.04482), metachronous distant metastases (P = 0.03131), death patient status (P = 0.000829), stage at diagnosis (P = 0.01995), and stage III/IV at last follow-up (P = 0.01552). TERT amplification associated independently with tumor-related recurrence and death. Our study shows that PTC can be stratified into clinically prognostic relevant categories based on the presence or not of TERT amplification in the cells.

Keywords: TERT amplification; Metastases; Prognosis; Survival; Thyroid cancer; Tumor recurrence.

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Conflict of interest statement

Declarations. Competing Interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Pattern of oncogenic activation in 21 PTCs with paired LNMs that did not develop DMs at diagnosis and/or during the follow-up (left hand side of the figure) and 20 PTCs with matching synchronous and/or metachronous DMs (right hand side of the figure). To facilitate the comprehension of the clonality or subclonality in the activation of the different oncogenic drivers, the pattern of tumor molecular heterogeneity, and the spread of the oncogenic events with metastatic PTC cells, all of the samples analyzed on each of the 41 PTC cases are shown. (a) Clinical-pathological features of the 41 patients including PTC subtype, histotype of each of the areas genotyped, sample type (pT, LNM, DM), age, sex, pT size, recurrence, timing of metastases (synchronous or metachronous), and survival status. Key colors are shown at the bottom of the figure. (b) Oncoprints of PTCs without DMs (left) and PTCs with DMs (right) including percentage of tumors altered on each driver. Key colors for genetic alterations found in the drivers investigated are shown boxed in the center of the figure. * RAS mutations are significantly correlated with PTCs with DMs. Fisher exact test two-tailed P = 0.003. # TERT amplification is significantly correlated with PTCs with DMs. Fisher exact test two-tailed P = 0.0448
Fig. 2
Fig. 2
Pattern of oncogenic activation in 15 PDCs (left hand side of the figure) and 35 ATCs (right hand side of the figure). To facilitate the comprehension of the clonality or subclonality in the activation of the different oncogenic drivers, the pattern of tumor molecular heterogeneity, the segregation of the oncogenic events with tumor dedifferentiation within the pT, and the spread of the oncogenic events with metastatic cells, all of the samples analyzed on each of the 15 PDC and 35 ATC cases are shown. (a) Clinical-pathological features of the 50 patients including histotype of each of the areas genotyped, sample type (pT, LNM, DM), age, sex, pT size, type of metastatic spread (LNM, DM, or both), recurrence, and survival status. Key colors are shown at the bottom of the figure. (b) Oncoprints of PDCs (left) and ATCs (right) including percentage of tumors altered on each driver. Key colors for genetic alterations found in the drivers investigated are shown boxed in the center of the figure. # TPM are significantly correlated with ATCs. Fisher exact test two-tailed P = 0.0299
Fig. 3
Fig. 3
Pattern of oncogenic activation in 13 thyroid cancer cell lines derived from pTs, LNMs, or DMs showing tumors with different degrees of differentiation (PTC, PDC, or ATC). (a) Clinical-pathological features including age and sex of the patient bearing the tumor from which they were derived, histotype of the tumor from which they were generated (PTC, PDC, or ATC), and organ (pT, LNM, or DM) from which they were derived. Key colors are shown boxed in the upper right margin. (b) Oncoprint including percentage of cell lines altered on each driver. Key colors for genetic alterations found in the drivers investigated are shown boxed in the lower right margin
Fig. 4
Fig. 4
Impact of TERT activation patterns on disease-related recurrence. Kaplan–Meier estimate of recurrence-free probability in PTC patients with information available regarding the exact moment of tumor relapse. Patients were dichotomized according to (a) the presence of TERT amplification; (b) the concurrence of TERT amplification and TPM; (c) the concurrence of TERT amplification and BRAF mutations; (d) the concurrence of TERT amplification and TPM and BRAF mutations; (e) the existence of TPM; (f) the presence of BRAF mutations; (g) the coexistence of TPM and BRAF mutations; and (h) the coexistence of TPM and BRAF mutations and RAS mutations
Fig. 5
Fig. 5
Impact of TERT activation patterns on disease-related survival. Kaplan–Meier estimate of likelihood of disease-related death in PTC patients with information available regarding the exact moment of DOD. Patients were dichotomized according to (a) the presence of TERT amplification; (b) the concurrence of TERT amplification and TPM; (c) the concurrence of TERT amplification and BRAF mutations; (d) the concurrence of TERT amplification and TPM and BRAF mutations; (e) the existence of TPM; and (f) the coexistence of TPM and BRAF mutations
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