Evaluation of MTAP and p16 immunohistochemical deficiency as surrogate marker for CDKN2A/B homozygous deletion in gliomas.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_EFBB413FD398
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Evaluation of MTAP and p16 immunohistochemical deficiency as surrogate marker for CDKN2A/B homozygous deletion in gliomas.
Périodique
Pathology
Auteur⸱e⸱s
Maragkou T., Reinhard S., Jungo P., Pasquier B., Neuenschwander M., Schucht P., Vassella E., Hewer E.
ISSN
1465-3931 (Electronic)
ISSN-L
0031-3025
Statut éditorial
Publié
Date de publication
06/2023
Peer-reviewed
Oui
Volume
55
Numéro
4
Pages
466-477
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Homozygous deletion (HD) of the CDKN2A/B locus has emerged as an unfavourable prognostic marker in diffuse gliomas, both IDH-mutant and IDH-wild-type. Testing for CDKN2A/B deletions can be performed by a variety of approaches, including copy number variation (CNV) analysis based on gene array analysis, next generation sequencing (NGS) or fluorescence in situ hybridisation (FISH), but questions remain regarding the accuracy of testing modalities. In this study, we assessed: (1) the utility of S-methyl-5'-thioadenosine phosphorylase (MTAP) and cellular tumour suppressor protein pl61NK4a (p16) immunostainings as surrogate markers for CDKN2A/B HD in gliomas, and (2) the prognostic value of MTAP, across different histological tumour grades and IDH mutation status. One hundred consecutive cases of diffuse and circumscribed gliomas (Cohort 1) were collected, in order to correlate MTAP and p16 expression with the CDKN2A/B status in the CNV plot of each tumour. IDH1 R132H, ATRX and MTAP immunohistochemistry was performed on next generation tissue microarrays (ngTMAs) of 251 diffuse gliomas (Cohort 2) for implementing survival analysis. Complete loss of MTAP and p16 by immunohistochemistry was 100% and 90% sensitive as well as 97% and 89% specific for CDKN2A/B HD, respectively, as identified on CNV plot. Only two cases (2/100) with MTAP and p16 loss of expression did not demonstrate CDKN2A/B HD in CNV plot; however, FISH analysis confirmed the HD for CDKN2A/B. Moreover, MTAP deficiency was associated with shortened survival in IDH-mutant astrocytomas (n=75; median survival 61 vs 137 months; p<0.0001), IDH-mutant oligodendrogliomas (n=59; median survival 41 vs 147 months; p<0.0001) and IDH-wild-type gliomas (n=117; median survival 13 vs 16 months; p=0.011). In conclusion, MTAP immunostaining is an important complement for diagnostic work-up of gliomas, because of its excellent correlation with CDKN2A/B status, robustness, rapid turnaround time and low costs, and provides significant prognostic value in IDH-mutant astrocytomas and oligodendrogliomas, while p16 should be used cautiously.
Mots-clé
Humans, Cyclin-Dependent Kinase Inhibitor p16/metabolism, Oligodendroglioma, Homozygote, DNA Copy Number Variations, Sequence Deletion, Gene Deletion, Glioma/diagnosis, Glioma/genetics, Biomarkers, Phosphorylases/genetics, Astrocytoma/diagnosis, Astrocytoma/genetics, Brain Neoplasms/diagnosis, Brain Neoplasms/genetics, Isocitrate Dehydrogenase/genetics, Mutation, CDKN2A/B homozygous deletion, CNV plot, Glioma, MTAP, p16
Pubmed
Web of science
Open Access
Oui
Création de la notice
11/04/2023 9:18
Dernière modification de la notice
27/06/2023 6:54
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