MTAP immunohistochemistry as a surrogate marker of CDKN2A loss in brain tumors: A meta-analysis and literature review.

in Journal of neuropathology and experimental neurology by Antonio Dono, Diego Pichardo-Rojas, Leonardo Mendoza Mora, Pavel S Pichardo-Rojas, Luis A Marin-Castañeda, Abril Carrillo, Adrian Coria Medrano, Yoshua Esquenazi, Leomar Y Ballester

TLDR

  • A meta-analysis evaluating 5'-methylthioadenosine phosphorylase (MTAP) expression as a surrogate of CDKN2A homozygous deletion (HD) found excellent sensitivity and specificity, suggesting its potential as a cost-effective and accessible method for identifying CDKN2A HD.

Abstract

Given the known relationship between CDKN2A homozygous deletion (HD) and worsened outcomes in both meningiomas and IDH-mutant astrocytomas, it is paramount to identify CDKN2A HD for accurate risk stratification of patients. Multiple array platforms can detect CDKN2A HD. However, these methods are expensive and are not readily available at every institution. To address this, we conducted a meta-analysis and literature review to evaluate 5'-methylthioadenosine phosphorylase (MTAP) expression determined by immunohistochemistry (IHC) as a surrogate of CDKN2A HD. Our study analyzed 7 cohort studies, 3 of which focused on meningiomas encompassing a total of 87 patients; and 4 studies were conducted on infiltrating glioma patients, consisting of 423 patients. Our results show that despite utilizing different MTAP IHC clones, the results among all studies showed consistently good sensitivity and specificity. The overall sensitivity and specificity of MTAP IHC as a surrogate of CDKN2A HD was excellent with 92.3% and 97.5%, respectively. These results were maintained when MTAP IHC was evaluated in distinct tumor types. MTAP IHC is a good surrogate marker for identifying CDKN2A HD in infiltrating gliomas and meningiomas. MTAP IHC implementation would allow correct integrated diagnosis for institutions that lack DNA sequencing.

Overview

  • The study aimed to evaluate the use of 5'-methylthioadenosine phosphorylase (MTAP) expression determined by immunohistochemistry (IHC) as a surrogate of CDKN2A homozygous deletion (HD) in patients with meningiomas and IDH-mutant astrocytomas.
  • The study analyzed 7 cohort studies, comprising 87 patients with meningiomas and 423 patients with infiltrating gliomas.
  • The primary objective was to identify a cost-effective and accessible method for identifying CDKN2A HD, which is essential for accurate risk stratification of patients.

Comparative Analysis & Findings

  • The study found that despite using different MTAP IHC clones, the results among all studies showed consistently good sensitivity and specificity for detecting CDKN2A HD.
  • The overall sensitivity and specificity of MTAP IHC as a surrogate of CDKN2A HD was excellent, with 92.3% and 97.5%, respectively.
  • The results were maintained when MTAP IHC was evaluated in distinct tumor types, suggesting that it can be a reliable method for identifying CDKN2A HD across different patient populations.

Implications and Future Directions

  • The study highlights the potential of MTAP IHC as a cost-effective and accessible method for identifying CDKN2A HD, which can be particularly useful for institutions that lack access to DNA sequencing.
  • Future studies can build on this research by exploring the use of MTAP IHC in other tumor types and evaluating its performance in combination with other diagnostic markers.
  • urther research is needed to fully understand the molecular mechanisms underlying CDKN2A HD and MTAP expression, and to identify potential therapeutic targets for improving patient outcomes.
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