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The Pathologist / Issues / 2025 / September / MYCN Amplification Predicts Poor Outcomes in Gliomas
Oncology Research and Innovations Omics

MYCN Amplification Predicts Poor Outcomes in Gliomas

Raised levels of proto-oncogene MYCN predict higher grade, epithelioid features, and reduced survival

By Kathryn Wighton 10/01/2025 News 2 min read

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In nearly 15 percent of isocitrate dehydrogenase-mutant gliomas, MYCN amplification was present and strongly associated with shorter survival, particularly in lower-grade tumors, according to a recent study.

Researchers evaluated the prognostic relevance of MYCN amplification in isocitrate dehydrogenase-mutant gliomas in a study published in  The Journal of Pathology Clinical Research. The cohort included 190 patients with isocitrate dehydrogenase (IDH)-mutant gliomas who underwent analysis of clinical, pathological, and molecular features. MYCN amplification status was determined using fluorescence in situ hybridization, and survival outcomes were assessed with Kaplan–Meier and multivariable Cox regression models.

In 28 of 190 cases (14.7 percent) MYCN amplification was identified. Amplification was significantly associated with higher tumor grade and elevated Ki-67 proliferation indices. Patients with MYCN-amplified gliomas had shorter overall survival compared with those without amplification (91.1 vs 112.1 months). This difference was most pronounced in lower-grade tumors, where survival decreased from 122.1 months in non-amplified cases to 47.8 months in amplified cases. Multivariable analysis confirmed MYCN amplification as an independent prognostic factor.

Morphological review showed that 50 percent of MYCN-amplified gliomas demonstrated epithelioid features, including eosinophilic cytoplasm and eccentrically positioned nuclei. Additional histological findings in amplified tumors included pseudopapillary patterns, vascular-like structures, necrosis, and microvascular proliferation.

Based on these findings, the researchers proposed a refined grading system in which lower-grade IDH-mutant astrocytomas with MYCN amplification would be reclassified as grade 4. This MYCN-based classification demonstrated improved prognostic stratification compared with the conventional World Health Organization system.

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Kathryn Wighton

Editor, Conexiant

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