Detection of ATRX and IDH1-R132H immunohistochemistry in the progression of 211 paired gliomas

Oncotarget. 2016 Mar 29;7(13):16384-95. doi: 10.18632/oncotarget.7650.

Abstract

Recurrence and progression to higher grade lesions are key biological events and characteristic behaviors in the evolution process of glioma. A small residual population of cells always escapes surgery and chemoradiation, resulting in a typically fatal tumor recurrence or progression. IDH mutation (isocitrate dehydrogenase) and ATRX (alpha-thalassemia/mental retardation, X-linked) loss/mutation occur in association and may represent early genetic alterations in the development of gliomas. However, their prognostic value in the evolution of gliomas still needs further investigation.Two hundreds and eleven serial sampling of gliomas were included in our study. We used immunohistochemistry (IHC) to detect IDH1-R132H mutation and ATRX status and showed that the IDH1-R132H and (or) ATRX status could be necessary to provide the basic molecular information for the "integrated diagnosis" of gliomas. We illustrated an evaluation formula for the evolution of gliomas by IDH1-R132H combined with ATRX immunohistochemistry and identified the association of IDH1-R132H/ATRX loss accompanied by longer progression time interval of patients with gliomas. Furthermore, we observed that most recurrences had a consistent IDH1 and ATRX status with their matched primary tumors and demonstrated the progressive pattern of grade II astrocytoma/oligodendroglial tumors and anaplastic oligoastrocytoma with or without IDH1-R132H. Identification of IDH1-R132H and ATRX loss status in the primary-recurrent gliomas may aid in treatment strategy selection, therapeutic trial design, and clinical prognosis evaluation.

Keywords: ATRX loss; IDH1-R132H; evolution; glioma; progression.

MeSH terms

  • Adult
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Disease Progression
  • Female
  • Glioma / diagnosis
  • Glioma / genetics*
  • Glioma / metabolism
  • Humans
  • Immunohistochemistry / methods
  • Isocitrate Dehydrogenase / genetics*
  • Isocitrate Dehydrogenase / metabolism
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Neoplasm Recurrence, Local
  • Prognosis
  • ROC Curve
  • Reproducibility of Results
  • X-linked Nuclear Protein / genetics*
  • X-linked Nuclear Protein / metabolism

Substances

  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • ATRX protein, human
  • X-linked Nuclear Protein