p16 Immunohistochemistry as a Screening Tool for Homozygous CDKN2A Deletions in CNS Tumors

Author:

Zschernack Valentina1,Andreiuolo Felipe12,Dörner Evelyn1,Wiedey Anna13,Jünger Stephanie T.14,Friker Lea L.1,Maruccia Riccardo1,Pietsch Torsten1

Affiliation:

1. Department of Neuropathology, DGNN Brain Tumor Reference Center

2. Instituto Estadual do Cérebro Paulo Niemeyer and the IDOR Institute, Rio de Janeiro, Brazil

3. Department of Neurology, University of Bonn Medical Center, Bonn

4. Department of Neurosurgery, University of Cologne Medical Center, Cologne, Germany

Abstract

The 2021 World Health Organization classification of tumors of the central nervous system emphasizes the significance of molecular parameters for an integrated diagnosis. Homozygous deletion of cyclin-dependent kinase inhibitor 2a (CDKN2A) has been associated with an adverse prognosis in IDH-mutant gliomas, supratentorial ependymomas, meningiomas, and MPNST. In this study, we examined the value of p16 protein immunohistochemistry as a rapid and cost-effective screening tool for a homozygous CDKN2A deletion. Genetic analyses for CDKN2A in 30 pleomorphic xanthoastrocytomas, 32 IDH-wild-type high-grade gliomas, 40 supratentorial ependymomas with ZFTA-RELA gene fusion, 21 IDH-mutant astrocytomas, and 24 meningiomas were performed mainly by a molecular inversion probe assay, a high-resolution, quantitative technology for the assessment of chromosomal copy number alterations. Immunohistochemistry for p16 proved to have a high positive predictive value (range 90% to 100%) and an overall low negative predictive value (range 22% to 93%) for a homozygous CDKN2A deletion. In a setting where molecular testing is limited for cost and time reasons, p16 immunohistochemistry serves as a useful and rapid screening tool for identifying cases that should be subjected to further molecular testing for CDKN2A deletions.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Pathology and Forensic Medicine,Surgery,Anatomy

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