Diagnostic Use of IDH1/2 Mutation Analysis in Routine Clinical Testing of Formalin-Fixed, Paraffin-Embedded Glioma Tissues

• Published in: Journal of neuropathology and experimental neurology Vol. 68; no. 12; pp. 1319 - 1325
• Main Authors: Horbinski, Craig, Kofler, Julia, Kelly, Lindsey M, Murdoch, Geoffrey H, Nikiforova, Marina N
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Association of Neuropathologists, Inc 01-12-2009; Lippincott Williams & Wilkins; Oxford University Press
• Subjects: Biological and medical sciences; Biomarkers, Tumor - genetics; Brain Neoplasms - genetics; DNA Mutational Analysis - methods; Formaldehyde; Glioma - genetics; Humans; Investigative techniques, diagnostic techniques (general aspects); Isocitrate Dehydrogenase - genetics; Medical sciences; Mutation; Nervous system; Neurology; Paraffin Embedding; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Polymerase Chain Reaction - methods; Tissue Fixation; Molecular genetics; Stereotactic biopsy; Dehydrogenase; Paraffin; Malignant glioma; Tissue; Genetics; Diagnosis; Child; Isocitrate dehydrogenase; Pediatric oligodendroglioma; Human; Nervous system diseases; Enzyme; Routine analysis; Stereotaxia; Malignant tumor; Oligodendroglioma; Ganglioglioma; Glioma; Biopsy; Paraffin sections; Central nervous system disease; Oxidoreductases; Mutation; Cancer
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1097/NEN.0b013e3181c391be

Mutations in isocitrate dehydrogenase enzyme isoforms 1 (IDH1) and 2 (IDH2) have been identified in many adult astrocytomas and oligodendrogliomas. These mutations are targeted to specific codons (e.g. R132 in IDH1 and R172 in IDH2), making assays to detect them in clinical specimens feasible. We describe a simple and accurate molecular assay for detection of IDH1/2 mutations on routine formalin-fixed paraffin-embedded tissues. Using this polymerase chain reaction-based assay, we tested 75 glial neoplasms and 57 nonneoplastic conditions that can mimic gliomas including radiation changes, viral infections, and infarcts. Of the gliomas, 37 (49%) were positive for IDH1 or IDH2 mutations; the most common mutation was IDH1 (97%). Two of 12 gangliogliomas were positive for IDH1 mutation, and both had unfavorable clinical outcomes (p < 0.03). None of the nonneoplastic cases were positive for IDH mutations. The assay detected IDH mutations in biopsy material containing mostly glioma and in concomitant near-miss stereotactic core biopsies that were otherwise equivocal for the presence of glioma by light microscopy. These results indicate that testing for IDH1/2 mutations can be effectively performed in a clinical setting and can enhance the accuracy of diagnosis of gliomas when traditional diagnostic methods are not definitive.