IDH1-associated primary glioblastoma in young adults displays differential patterns of tumour and vascular morphology

PLoS One. 2013;8(2):e56328. doi: 10.1371/journal.pone.0056328. Epub 2013 Feb 22.

Abstract

Glioblastoma is a highly aggressive tumour with marked heterogeneity at the morphological level in both the tumour cells and the associated highly prominent vasculature. As we begin to develop an increased biological insight into the underlying processes driving the disease, fewer attempts have thus far been made to understand these phenotypic differences. We sought to address this by carefully assessing the morphological characteristics of both the tumour cells and the associated vasculature, relating these observations to the IDH1/MGMT status, with a particular focus on the early onset population of young adults who develop primary glioblastoma. 276 primary glioblastoma specimens were classified into their predominant cell morphological type (fibrillary, gemistocytic, giant cell, small cell, oligodendroglial, sarcomatous), and assessed for specific tumour (cellularity, necrosis, palisades) and vascular features (glomeruloid structures, arcades, pericyte proliferation). IDH1 positive glioblastomas were associated with a younger age at diagnosis, better clinical outcome, prominent oligodendroglial and small cell tumour cell morphology, pallisading necrosis and glomeruloid vascular proliferation in the absence of arcade-like structures. These features widen the phenotype of IDH1 mutation-positive primary glioblastoma in young adults and provide correlative evidence for a functional role of mutant IDH1 in the differential nature of neo-angiogenesis in different subtypes of glioblastoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology*
  • Humans
  • Immunohistochemistry
  • Isocitrate Dehydrogenase / metabolism*
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Pathologic / pathology*
  • Tissue Array Analysis
  • Young Adult

Substances

  • Isocitrate Dehydrogenase
  • IDH1 protein, human

Grants and funding

JMJ is an employee of AstraZeneca. CJ receives research grant funding from AstraZeneca. SP, AJ, SEL, AB and CJ acknowledge NHS funding to the Biomedical Research Centre. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.