Poor diagnostic value of isocitrate dehydrogenase 1 R132H immunohistochemistry for determination of isocitrate dehydrogenase 1 status in patients with glioblastoma.

Abstract

Background: The World Health Organization (WHO) classification of central nervous system (CNS) tumors is a major advance toward improving the diagnosis of adult brain tumors. Despite the promise of isocitrate dehydrogenase (IDH) mutations as an important biomarker for glioblastoma, not all institutions have ready access to mutation detection polymerase chain reaction (PCR) methods, and deoxyribonucleic acid (DNA) sequencing may be problematic in very small biopsies. However, a simultaneous evaluation of IDH1 status by DNA sequencing and immunohistochemistry (IHC) to determine the sensitivity and specificity of both methods, along with their predictive value, was unavailable.

Methods: This retrospective study included 33 patients who underwent surgical resection or biopsy, January 2016-December 2019. The diagnosis of glioblastoma was established. Surgically resected tumor tissues were fixated in 10%-formaldehyde preserved in paraffin-embedded blocks. Glioblastoma was classified according to the 2021 WHO classification of CNS tumors. The enrolled patients were followed up to obtain the overall survival rate (median follow-up time, 30 months).

Results: Thirty-three patients (14 male; 19 female), mean age of 44.74 ± 15.49 years. Eight had WHO Grade II, 2 with WHO Grade III, and 23 with WHO Grade IV. The sensitivity and specificity of IDH1 IHC were 81.82% (P = 0.0007), a positive predictive value of 90.00% (69.90-98.22%), and a negative predictive value of 69.23% (42.37-87.32%). The survival rate was significantly higher in IDH1 mutant than wild-type IDH1, whether based on IHC or PCR (P = 0.0014).

Conclusion: IDH1 status evaluation is crucial to predicting the survival rate and important for guiding the treatment decision for patients with glioblastoma. Despite the lesser sensitivity and specificity of IHC in comparison to DNA sequencing in this study, larger prospective studies are needed to validate our preliminary finding.