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. 2023 May;27(3):371-381.
doi: 10.1007/s40291-022-00638-7. Epub 2023 Jan 23.

Clinical Evaluation of IDH Mutation Status in Formalin-Fixed Paraffin-Embedded Tissue in Gliomas

Ernest J Nelson  1 , Maria A Gubbiotti  1 , Alicia M Carlin  1 , MacLean P Nasrallah  1 , Vivianna M Van Deerlin  1 , Sarah E Herlihy  2
Affiliations

Clinical Evaluation of IDH Mutation Status in Formalin-Fixed Paraffin-Embedded Tissue in Gliomas

Ernest J Nelson et al. Mol Diagn Ther. 2023 May.

Abstract

Background and objective: Determination of isocitrate dehydrogenase (IDH) 1/2 mutational status is crucial for a glioma diagnosis. It is common for IDH mutational status to be determined via a two-step algorithm that utilizes immunohistochemistry studies for IDH1 R132H, the most frequent variant, followed by next-generation sequencing studies for immunohistochemistry-negative or immunohistochemistry-equivocal cases. The objective of this study was to evaluate adding a rapid real-time polymerase chain reaction (RT-PCR) assay to the testing algorithm. METHODS: We validated a modified, commercial, qualitative, RT-PCR assay with the ability to detect 14 variants in IDH1/2 in formalin-fixed paraffin-embedded glioma tumor specimens. The assay was validated using 51 tumor formalin-fixed paraffin-embedded specimens. During clinical implementation of this assay, 48 brain tumor specimens were assessed for IDH result concordance and turnaround time to result.

Results: Concordance between the RT-PCR and sequencing and IHC studies was 100%. This RT-PCR assay also showed concordant results with IHC for IDH1 R132H for 11 of the 12 (92%) tumor specimens with IDH mutations. The RT-PCR assay yielded faster results (average 2.6 days turnaround time) in comparison to sequencing studies (17.9 days), with complete concordance.

Conclusions: In summary, we report that this RT-PCR assay can reliably be performed on formalin-fixed paraffin-embedded specimens and has a faster turnaround time than sequencing assays and can be clinically implemented for determination of IDH mutation status for patients with glioma.

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Conflict of interest statement

Abbott Molecular Inc. sponsored Sarah E. Herlihy for a Lab Roots lecture of the validation data presented in this article. All data validation and analysis were completed prior to the service initiation. Ernest J. Nelson, Maria A. Gubbiotti, Alicia M. Carlin, MacLean P. Nasrallah, Vivianna M. Van Deerlin have no conflicts of interest that are directly relevant to the content of this article.

Figures

Fig. 1
Fig. 1
Comparison of turnaround time (TAT) to diagnosis from having immunohistochemistry (IHC) -> next-generation sequencing versus including real-time polymerase chain reaction (RT-PCR). The first sequence depicts the two-step algorithm utilized for determination of isocitrate dehydrogenase (IDH) mutation status for glioma tumor specimens, which includes IHC studies for IDH1 R132H with follow-up sequencing studies. The second sequence shows an alternative algorithm that utilizes the RT-PCR assay to determine IDH mutation status and has a faster average TAT than sequencing studies. Avg average, SD standard deviation
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