Immunohistochemical ATRX expression is not a surrogate for 1p19q codeletion

Area of Science:

• Neuro-oncology
• Molecular Pathology
• Cancer Genomics

Background:

• The isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion (codel) are crucial for diagnosing and prognosing lower-grade gliomas.
• ATRX mutations and 1p/19q codel are typically mutually exclusive, suggesting ATRX immunohistochemistry (IHC) could potentially replace 1p/19q codel testing.

Purpose of the Study:

• To comprehensively evaluate the reliability of ATRX-IHC as a surrogate marker for 1p/19q codel status in IDH-mutant lower-grade gliomas.
• To assess the diagnostic discrepancies between ATRX-IHC and genetic testing for 1p/19q codel.

Main Methods:

• Performed ATRX-IHC on 78 gliomas with confirmed ATRX status via whole exome sequencing.
• Compared diagnostic classifications based on IDH status and ATRX-IHC alone versus those including 1p/19q codel testing.

Main Results:

• ATRX-IHC showed inconsistency with actual ATRX mutational patterns.
• Using IDH status and ATRX-IHC for diagnosis led to misclassification in 14% (11 of 78) of cases when compared to 1p/19q codel testing.
• Specifically, 11 out of 64 IDH-mutant gliomas demonstrated dissociation between ATRX-IHC and 1p/19q codel status.

Conclusions:

• ATRX-IHC is not a fully reliable surrogate for 1p/19q codel status in lower-grade gliomas.
• Caution is advised when relying solely on ATRX-IHC for tumor subtyping due to observed discrepancies with genetic testing.
• Accurate molecular subtyping of gliomas necessitates direct testing for 1p/19q co-deletion.