# Consequences of Hypoxic Events, Necrosis, and Microvascular Density, in Astrocytoma IDH-Mutant, CNS WHO Grade 4

## TL;DR

This study explores how hypoxia-related features like necrosis and microvascular density affect survival in a specific type of brain tumor called IDH-mutant astrocytoma.

## Contribution

The study identifies hypoxia-induced necrosis and microvascular density as key prognostic factors linked to tumor aggressiveness and survival in IDH-mutant CNS grade 4 astrocytoma.

## Key findings

- Necrosis and microvascular density are negative risk factors for patient survival.
- p53 overexpression, PTEN loss, and CDKN2A gene changes are associated with tumor aggressiveness.
- Increased resectability is a protective factor, while residual tumor volume negatively impacts survival.

## Abstract

Background/Objectives: Astrocytoma IDH-mutant CNS WHO grade 4 is a malignant tumor of the central nervous system characterized by tumor necrosis, microvascular proliferation, and/or homozygous CDKN2A/B deletion. This study aims to investigate the prognostic role of the consequences of hypoxic events leading to necrosis and microvascular density, observing their associations with clinical-imaging parameters and morphogenetics. Methods: We performed a retrospective analysis over a 10-year period. Clinical and imaging data were collected from observation sheets and electronic databases. Six immunohistochemical markers and FISH testing were used to evaluate the prognosis and neoformation of blood vessels. Based on the whole slide image, the necrotic percentage was assessed, and the microvascular density was quantified. All data were statistically analyzed. Results: We identified 44 cases, with a mean age of 57.86 years. From a clinical perspective, advanced age, arterial hypertension, diabetes mellitus, and acute onset of clinical manifestations represent negative prognostic factors. In imaging, the increased rate of resectability is a protective factor, while the presence of residual volume and an increased residual volume have a negative impact on survival. The consequences of hypoxic events (tumor necrosis and microvascular density) are negative risk factors for survival. Added to these are p53 overexpression, loss of PTEN, deletion, and amplification of the CDKN2A gene. Conclusions: We observed that necrosis and increased microvascular density resulting from microvascular proliferation are both defining features of the tumor and impact patient prognosis and survival. In addition, they induce or are associated with other essential changes (p53, PTEN, CDKN2A) that promote tumor aggressiveness.