TERT Promoter Mutations and Tert Expression in Early-Stage (T1N0M0) Non-Small Cell Lung Cancer (NSCLC)

Abstract

Background: The mutations detected in the promoter of the telomerase reverse transcriptase (TERT) gene, namely C228T and C250T, were first identified in melanoma and subsequently in several cancer models, notably glioma, thyroid cancer and bladder cancer. Recent findings demonstrate that mutation of the TERT promoter may be one of the most common genetic mechanisms contributing to telomerase activation in malignant cells. Mutation of the TERT promoter appears to be an indicator of worse outcome and is correlated with tumor aggressiveness and patient survival; however, to date the only two published studies reported a very low TERT mutation frequency in non-small cell lung cancer (NSCLC). Additionally, the relationship among the presence of these mutations, Tert expression and clinical outcome is unknown.

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

“…As our literature review revealed, several studies encompassing a total of 645 oncology patients and 4 different TERT IHC antibodies demonstrated that the sensitivity (50% to 76.2%) and specificity (45% to 68.1%) are poor compared with sequencing 18–22. This lack of association between TERT IHC and TERT p mutations has also been observed in studies evaluating non–small cell carcinoma and thyroid cancer, even after the evaluation of different scoring systems 23,24. Importantly, a prior study evaluating TERT IHC using a monoclonal antibody (TMab-6) in glioma showed that TERT expression was elevated in both TERT WT and mutant tumor tissue and vasculature 20.…”

“…[18][19][20][21][22] This lack of association between TERT IHC and TERTp mutations has also been observed in studies evaluating non-small cell carcinoma and thyroid cancer, even after the evaluation of different scoring systems. 23,24 Importantly, a prior study evaluating TERT IHC using a monoclonal antibody (TMab-6) in glioma showed that TERT expression was elevated in both TERT WT and mutant tumor tissue and vasculature. 20 Moreover, a study evaluating TERT A-6 antibody (Santa Cruz Biotechnology) in glioma demonstrated poor sensitivity and specificity of this IHC assay for TERTp mutations.…”