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 Z. Powell, J. Clay Goodman, Gregory N. Fuller

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 1 2012
Externally publishedYes

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Isocitrate Dehydrogenase
Glioma
Glioblastoma
Mutation
Germany
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Absence of IDH1-R132H mutation predicts rapid progression of nonenhancing diffuse glioma in older adults. / Olar, Adriana; Raghunathan, Aditya; Albarracin, Constance T.; Aldape, Kenneth D.; Cahill, Daniel P.; Powell, Suzanne Z.; Goodman, J. Clay; Fuller, Gregory N.

In: Annals of Diagnostic Pathology, Vol. 16, No. 3, 01.06.2012, p. 161-170.

Research output: Contribution to journalArticle

Olar, Adriana ; Raghunathan, Aditya ; Albarracin, Constance T. ; Aldape, Kenneth D. ; Cahill, Daniel P. ; Powell, Suzanne Z. ; Goodman, J. Clay ; Fuller, Gregory N. / Absence of IDH1-R132H mutation predicts rapid progression of nonenhancing diffuse glioma in older adults. In: Annals of Diagnostic Pathology. 2012 ; Vol. 16, No. 3. pp. 161-170.
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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.",
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AU - Cahill, Daniel P.

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