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IDH1 Mutations in Diffusely Infiltrating Astrocytomas
Grade Specificity, Association With Protein Expression, and Clinical Relevance

Balaram Thota MSc, Sudhanshu K. Shukla MSc, Mallavarapu R. Srividya MSc, Shivayogi D. Shwetha MSc, Arimappamagan Arivazhagan MS, MCh, Kandavel Thennarasu PhD, Yasha T. Chickabasaviah MD, Alangar S. Hegde MCh, PhD, Bangalore A. Chandramouli MCh, Kumarvel Somasundaram PhD, Vani Santosh MD
DOI: http://dx.doi.org/10.1309/AJCPZOIY3WY4KIKE 177-184 First published online: 1 August 2012


IDH1 mutations are frequent genetic alterations in low-grade diffuse gliomas and secondary glioblastoma (GBM). To validate mutation frequency, IDH1 gene at codon 132 was sequenced in 74 diffusely infiltrating astrocytomas: diffuse astrocytoma (DA; World Health Organization [WHO] grade II), anaplastic astrocytoma (AA; WHO grade III), and GBM (WHO grade IV). All cases were immunostained with IDH1-R132H monoclonal antibody. Mutational status was correlated with mutant protein expression, patient age, duration of symptoms, and prognosis of patients with GBM. We detected 31 (41.9%) heterozygous IDH1 mutations resulting in arginine-to-histidine substitution (R132H;CGT-CAT). All 12 DAs (100%), 13 of 14 AAs (92.9%), and 6 of 48 GBMs (12.5%) (5/6 [83.3%] secondary, and 1/42 [2.4%] primary) harbored IDH1 mutations. The correlation between mutational status and protein expression was significant (P < . 001). IDH1 mutation status, though not associated with prognosis of patients with GBM, showed significant association with younger age and longer duration of symptoms in the whole cohort (P < .001). Our study validates IDH1 mutant protein expression across various grades of astrocytoma, and demonstrates a high incidence of IDH1 mutations in DA, AA, and secondary GBM.

Key Words
  • Immunohistochemistry
  • IDH1
  • Astrocytoma
  • Somatic mutation
  • Prognosis
  • DNA sequencing
  • Survival

Upon completion of this activity you will be able to:

  • list the IDH1 mutation that is most common in infiltrating glial neoplasms.

  • describe the physiologic effects associated with the IHD1 mutation.

  • predict the frequency of IDH1 mutation expected in different types of glial neoplasms, including comparison of primary from secondary glioblastoma multiforme.

The ASCP is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASCP designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™ per article. Physicians should claim only the credit commensurate with the extent of their participation in the activity. This activity qualifies as an American Board of Pathology Maintenance of Certification Part II Self-Assessment Module.

The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.

Questions appear on p 305. Exam is located at www.ascp.org/ajcpcme.

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