HIP1R and vimentin immunohistochemistry predict 1p/19q status in IDH-mutant glioma

• Verfasst von: Felix, Marius [VerfasserIn]
• Verfasst von: Friedel, Dennis [VerfasserIn]
• Verfasst von: Jayavelu, Ashok Kumar [VerfasserIn]
• Verfasst von: Filipski, Katharina Johanna [VerfasserIn]
• Verfasst von: Reinhardt, Annekathrin [VerfasserIn]
• Verfasst von: Warnken, Uwe [VerfasserIn]
• Verfasst von: Stichel, Damian [VerfasserIn]
• Verfasst von: Schrimpf, Daniel [VerfasserIn]
• Verfasst von: Korshunov, Andrey [VerfasserIn]
• Verfasst von: Wang, Yueting [VerfasserIn]
• Verfasst von: Keßler, Tobias [VerfasserIn]
• Verfasst von: Etminan, Nima [VerfasserIn]
• Verfasst von: Unterberg, Andreas [VerfasserIn]
• Verfasst von: Herold-Mende, Christel [VerfasserIn]
• Verfasst von: Heikaus, Laura [VerfasserIn]
• Verfasst von: Sahm, Felix [VerfasserIn]
• Verfasst von: Wick, Wolfgang [VerfasserIn]
• Verfasst von: Harter, Patrick Nikolaus [VerfasserIn]
• Verfasst von: Deimling, Andreas von [VerfasserIn]
• Verfasst von: Reuss, David [VerfasserIn]
• Titel: HIP1R and vimentin immunohistochemistry predict 1p/19q status in IDH-mutant glioma
• Verf.angabe: Marius Felix, Dennis Friedel, Ashok Kumar Jayavelu, Katharina Filipski, Annekathrin Reinhardt, Uwe Warnken, Damian Stichel, Daniel Schrimpf, Andrey Korshunov, Yueting Wang, Tobias Kessler, Nima Etminan, Andreas Unterberg, Christel Herold-Mende, Laura Heikaus, Felix Sahm, Wolfgang Wick, Patrick N. Harter, Andreas von Deimling, and David E. Reuss
• E-Jahr: 2022
• Jahr: 03 May 2022
• Umfang: 12 S.
• Fussnoten: Gesehen am 05.06.2023
• Titel Quelle: Enthalten in: Neuro-Oncology
• Ort Quelle: Oxford : Oxford Univ. Press, 1999
• Jahr Quelle: 2022
• Band/Heft Quelle: 24(2022), 12 vom: Dez., Seite 2121-2132
• ISSN Quelle: 1523-5866
• DOI: doi:10.1093/neuonc/noac111
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1847387810

Abstract

IDH-mutant gliomas are separate based on the codeletion of the chromosomal arms 1p and 19q into oligodendrogliomas IDH-mutant 1p/19q-codeleted and astrocytomas IDH-mutant. While nuclear loss of ATRX expression excludes 1p/19q codeletion, its limited sensitivity prohibits to conclude on 1p/19q status in tumors with retained nuclear ATRX expression.Employing mass spectrometry based proteomic analysis in a discovery series containing 35 fresh frozen and 72 formalin fixed and paraffin embedded tumors with established IDH and 1p/19q status, potential biomarkers were discovered. Subsequent validation immunohistochemistry was conducted on two independent series (together 77 oligodendrogliomas IDH-mutant 1p/19q-codeleted and 92 astrocytomas IDH-mutant).We detected highly specific protein patterns distinguishing oligodendroglioma and astrocytoma. In these patterns, high HIP1R and low vimentin levels were observed in oligodendroglioma while low HIP1R and high vimentin levels occurred in astrocytoma. Immunohistochemistry for HIP1R and vimentin expression in 35 cases from the FFPE discovery series confirmed these findings. Blinded evaluation of the validation cohorts predicted the 1p/19q status with a positive and negative predictive value as well as an accuracy of 100% in the first cohort and with a positive predictive value of 83%; negative predictive value of 100% and an accuracy of 92% in the second cohort. Nuclear ATRX loss as marker for astrocytoma increased the sensitivity to 96% and the specificity to 100%.We demonstrate that immunohistochemistry for HIP1R, vimentin, and ATRX predict 1p/19q status with 100% specificity and 95% sensitivity and therefore, constitutes a simple and inexpensive approach to the classification of IDH-mutant glioma.