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

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

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, fol...

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Bibliographic Details
Published in:Molecular diagnosis & therapy Vol. 27; no. 3; pp. 371 - 381
Main Authors: Nelson, Ernest J., Gubbiotti, Maria A., Carlin, Alicia M., Nasrallah, MacLean P., Van Deerlin, Vivianna M., Herlihy, Sarah E.
Format: Journal Article
Language:English
Published: Cham Springer International Publishing 01-05-2023
Springer Nature B.V
Subjects:
Algorithms
Assaying
Biomedical and Life Sciences
Biomedicine
Brain cancer
Brain Neoplasms - genetics
Brain tumors
Cancer Research
Dehydrogenases
DNA methylation
Enzymes
Epigenetics
Evaluation
FDA approval
Formaldehyde
Glioma
Glioma - genetics
Human Genetics
Humans
Immunohistochemistry
Isocitrate dehydrogenase
Isocitrate Dehydrogenase - genetics
Laboratory Medicine
Medical prognosis
Molecular Medicine
Mutation
Next-generation sequencing
Original
Original Research Article
Paraffin
Paraffin Embedding
Paraffins
Pharmacotherapy
Polymerase chain reaction
Tumors
United States > US
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Summary: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.
ISSN:1177-1062
1179-2000
DOI:10.1007/s40291-022-00638-7