TERT amplification a risk stratification marker in papillary thyroid carcinoma, significantly correlated with tumor recurrence and survival

Abstract

Few studies have analyzed the prevalence of TERT amplification in thyroid cancer, showing discrepancies in various top- ics. 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 dediffer- entiation 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 diag- nosis (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.