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

Author:

Dono Antonio12,Moosvi Ali M.1,Goli Puneetha S.1,Bellman Allison C.1,Aung Phyu P.3,Esquenazi Yoshua245,Ballester Leomar Y.136

Affiliation:

1. Department of Pathology and Laboratory Medicine

2. Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston

3. Pathology

4. Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston

5. Memorial Hermann Hospital—TMC, Houston, TX

6. Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center

Abstract

Genomic alterations are critical for the diagnosis, prognostication, and treatment of patients with infiltrating gliomas. Telomerase reverse transcriptase promoter (TERTp) mutations are among such crucial alterations. Although DNA sequencing is the preferred method for identifying TERTp mutations, it has limitations related to cost and accessibility. We tested telomerase reverse transcriptase (TERT) immunohistochemistry (IHC) as a surrogate for TERTp 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 TERTp mutations was performed. Eighteen gliomas harbored TERTp mutations. Overall, TERT IHC demonstrated a sensitivity of 61.1% and a specificity of 69.2% for identifying TERTp mutations. Among the 19 IDH1/IDH2-wild-type gliomas, 16 (84%) harbored TERTp 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 TERTp 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 TERTp 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 TERTp mutations. TERT IHC is a suboptimal surrogate marker for TERTp mutations in infiltrating gliomas. The need remains for cost-effective, efficient, and accessible alternatives to next-generation sequencing for the evaluation of TERTp mutations in gliomas.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Medical Laboratory Technology,Histology,Pathology and Forensic Medicine

Reference27 articles.

1. Understanding TERT promoter mutations: a common path to immortality;Bell;Mol Cancer Res,2016

2. The solo play of TERT promoter mutations;Hafezi;Cells,2020

3. Telomere maintenance mechanisms in cancer;Gaspar;Genes (Basel),2018

4. TERT—regulation and roles in cancer formation;Dratwa;Front Immunol,2020

5. IDH1 and IDH2 mutations in gliomas;Yan;N Engl J Med,2009

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