TERT Immunohistochemistry Expression as a Surrogate of TERT Promoter Mutations in Infiltrating Gliomas

Abstract

Introduction/Objective: Genomic alterations are critical for the diagnosis of infiltrating gliomas. Mutations in the telomerase reverse transcriptase promoter (TERTp) are sufficient for a diagnosis of glioblastoma in some cases, independent of histologic features. Although DNA sequencing is the preferred method for evaluating TERTp mutations, there are limitations with regards to turnaround-time, accessibility, and cost. In this study, we evaluated the efficacy of using TERT immunohistochemistry (IHC) as a surrogate marker for the identification of TERTp mutations in infiltrating gliomas. Methods/Case Report: The study cohort consisted of 31 infiltrating gliomas diagnosed following the 2016 WHO classification of CNS tumors by a board-certified neuropathologist. Each case was evaluated by immunohistochemistry (anti-TERT monoclonal antibody) and with a targeted next-generation sequencing (NGS) panel. A systemic literature search was conducted to examine reports of TERT antibody as a surrogate marker of TERTp mutations. TERTp mutation detected by sequencing was considered the gold standard. Results (if a Case Study enter NA): TERT immunohistochemistry demonstrated a sensitivity of 61.1% and specificity of 69.2%. Cases were divided into IDH-WT and IDH-mutant infiltrating gliomas. Among the IDH-WT group, 84% contained the TERTp mutation with a sensitivity of 62.5% and specificity of 33.3% for the TERTp IHC. IDH-mutant gliomas showed a 16.2% TERTp mutation rate, and immunohistochemistry had a sensitivity of 50% and 80% specificity. The probability of TERT immunohistochemistry in diagnosing TERTp mutations exhibited a poor likelihood ratio for both the positive and negative test. Literature review included 5 studies with an overall sensitivity and specificity remaining consistently low (<80%), with 2 of these studies evaluating CNS related tumors giving rise to similar diagnostic performance. Conclusion: TERT IHC has suboptimal sensitivity and specificity for identifying TERTp mutations in IDH-WT and IDH-mutant infiltrating gliomas.