Absence of IDH1-R132H mutation predicts rapid progression of nonenhancing diffuse glioma in older adults

Adriana Olar, Aditya Raghunathan, Constance T. Albarracin, Kenneth D. Aldape, Daniel P. Cahill, Suzanne Zein-Eldin Powell, J. Clay Goodman, Gregory N. Fuller

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Advanced age and contrast enhancement portend a poor prognosis in diffuse glioma (DG). Diffuse glioma may present as nonenhancing tumors that rapidly progress in weeks to months to a pattern of ring enhancement, characteristic of glioblastoma (GBM). Mutations involving isocitrate dehydrogenase 1 (IDH1) have recently emerged as important diagnostic and prognostic markers in DG. R132H is the most common mutation, expressed in more than 80% of DG and secondary GBM but in less than 10% of primary GBM. Adults older than 50 years with nonenhancing, rapidly progressing DG were identified. A comparison group comprised randomly selected, age-matched patients with nonenhancing, nonprogressing DG. Isocitrate dehydrogenase 1 status was evaluated using anti-IDH1-R132H antibodies (Dianova, Hamburg, Germany). The results were correlated with the clinical outcomes. We identified 4 patients who presented with nonenhancing DG that rapidly progressed to ring-enhancing lesions that were subsequently diagnosed on surgical resection as GBM. This group showed absent IDH1-R132H expression, which is characteristic of primary GBM. The comparison group of 5 patients presented with nonenhancing, nonprogressing DG, and all 5 tumors showed IDH1-R132H expression. In conclusion, negative IDH1-R132H mutation status in nonenhancing DG of older adults is a poor prognostic factor associated with rapid progression to ring-enhancing GBM. The shorter interval of progression and negative IDH1-R132H mutation status suggest a similar molecular pathway as seen in primary GBM.

Original languageEnglish (US)
Pages (from-to)161-170
Number of pages10
JournalAnnals of Diagnostic Pathology
Volume16
Issue number3
DOIs
StatePublished - Jun 2012

Keywords

  • Glioma
  • IDH1-R132H
  • Nonenhancing
  • Older adults
  • Prognosis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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