The Diagnostic Value of MTAP Expression as a Surrogate for CDKN2A Deletion in Glioma and Meningioma: A Comprehensive Systematic Review and Meta-analysis
Diego Pichardo-Rojas1, Leonardo Mora2, Luis Marin-Castañeda3, Abril Carrillo4, Pavel S Pichardo-Rojas5
1Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", 2Universidad de Guadalajara, 3Facultad Mexicana de Medicina, 4Department of Internal Medicine, University of Texas Southwestern Medical Center, 5Vivian L. Smith Department of Neurosurgery, The University of Texas Health Science Center at Houston
Objective:
Conducting a meta-analysis is crucial in discerning the true efficacy and reliability of MTAP as a surrogate marker for CDKN2A HD.
Background:
The homozygous deletion (HD) of the CDKN2A gene is an unfavorable prognostic marker for resistance to treatment and shortened survival in brain tumors. CDKN2A HD frequently co-occurs with the loss of methylthioadenosine phosphorylase (MTAP) expression. This concurrent loss provides a viable opportunity for utilizing a negative MTAP immunohistochemistry (MTAP IHC) as a surrogate marker for CDKN2A HD in gliomas and meningiomas, MTAP being a more economic and widely-available alternative.
Design/Methods:
A database search was conducted until March 3rd, 2024 to identify studies that reported on the co-occurrence of CDKN2A HD and MTAP expression loss in adult-type gliomas and meningiomas. The primary outcomes analyzed included the sensitivity and specificity of MTAP expression as a surrogate marker for CDKN2A HD.
Results:
Out of 236 articles, 5 retrospective cohort studies met our inclusion criteria, considering 338 patients for analysis. For all included tumors, the positive predictive value (PPV) of a negative MTAP for a CDKN2A HD was 94.2% (95% CI 88.2%- 99.3%), while the negative predictive value (NPV) of a persistent MTAP for a retained CDKN2A was (95% CI=94.8%-99.5%). The sensitivity and specificity of MTAP deletion to CDKN2A HD in IDH-wildtype gliomas was 94.1% (95% CI=85.4%-102.8%) and 98.3% (95% CI=94.8%-101.7%) respectively.
Conclusions:
This meta-analysis suggests that a negative MTAP IHC can be a highly reliable surrogate marker for CDKN2A HD, particularly for meningiomas and IDH-wildtype gliomas. MTAP IHC can potentially serve as a useful prognostic tool in resource-limited settings, helping bridge the inequity gap between neurooncologic care in high and low-income communities. More studies are required to validate the use of MTAP IHC in tumor prognosis.
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