TERT Immunohistochemistry as a Surrogate Marker for TERT Promoter Mutations in Infiltrating Gliomas

Authors

Antonio Dono
Ali M Moosvi
Puneetha S Goli
Allison C Bellman
Phyu P Aung
Yoshua Esquenazi
Leomar Y Ballester

Publication Date

5-1-2023

Journal

Applied Immunohistochemistry & Molecular Morphology

Abstract

Genomic alterations are critical for the diagnosis, prognostication, and treatment of patients with infiltrating gliomas. Telomerase reverse transcriptase promoter ( TERT p) mutations are among such crucial alterations. Although DNA sequencing is the preferred method for identifying TERT p mutations, it has limitations related to cost and accessibility. We tested telomerase reverse transcriptase (TERT) immunohistochemistry (IHC) as a surrogate for TERT p mutations in infiltrating gliomas. Thirty-one infiltrating gliomas were assessed by IHC using an anti-TERT Y182 antibody. IHC results were analyzed by a board-certified neuropathologist. Tumors were analyzed by targeted next-generation sequencing. A literature review of the use of TERT antibodies as a surrogate for TERT p mutations was performed. Eighteen gliomas harbored TERT p mutations. Overall, TERT IHC demonstrated a sensitivity of 61.1% and a specificity of 69.2% for identifying TERT p mutations. Among the 19 IDH1/IDH2 -wild-type gliomas, 16 (84%) harbored TERT p mutations, and TERT IHC had a sensitivity of 62.5% and a specificity of 33.3%. Among the 12 IDH1/IDH2 -mutant gliomas, 2 (17%) harbored TERT p mutations, and TERT IHC had a sensitivity of 50% and a specificity of 80%. TERT IHC had low positive and negative likelihood values in the identification of TERT p mutations. The literature review included 5 studies with 645 patients and 4 different TERT antibodies. The results consistently showed poor sensitivity and specificity of TERT IHC for identifying TERT p mutations. TERT IHC is a suboptimal surrogate marker for TERT p mutations in infiltrating gliomas. The need remains for cost-effective, efficient, and accessible alternatives to next-generation sequencing for the evaluation of TERT p mutations in gliomas.

Keywords

TERT IHC, infiltrating glioma, TERT promoter mutation, TERT c.−124C > T, TERT c.−146C > T, glioblastoma, oligodendroglioma