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Correlation of MTAP immunohistochemical deficiency with CDKN2A homozygous deletion and clinicopathological features in pleomorphic xanthoastrocytoma

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Abstract

Pleomorphic xanthoastrocytoma (PXA) is a rare tumor ranging from World Health Organization (WHO) grades 2–3 and can potentially recur and metastasize throughout the central nervous system (CNS). Cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletion is a frequent genomic alteration of PXA. Methylthioadenosine phosphorylase (MTAP) immunohistochemistry is a promising surrogate marker for CDKN2A homozygous deletion in different cancers but has not been examined in PXA. Therefore, we performed CDKN2A fluorescence in situ hybridization and MTAP immunohistochemistry on specimens from 23 patients with CNS WHO grades 2 (n = 10) and 3 (n = 13) PXAs, including specimens from primary and recurrent tumors, and determined whether MTAP immunohistochemistry correlated with CDKN2A homozygous deletion and clinicopathological features. CDKN2A homozygous deletion was detected in 30% (3/10) and 76.9% (10/13) of CNS WHO grades 2 and 3 PXAs, respectively. In addition, MTAP loss was inconsistent with CDKN2A homozygous deletion (sensitivity = 86.7%, specificity = 100%). Furthermore, CDKN2A homozygous deletion was correlated with WHO grade (p = 0.026) and the Ki-67 labeling index (p = 0.037). Therefore, MTAP immunostaining can be a suitable surrogate marker for CDKN2A homozygous deletions in PXAs, and CDKN2A homozygous deletions may be an important prognostic factor for PXAs.

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Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

The project was supported by Hebei Natural Science Foundation (H2019206709), the Medical Applicable Technology Tracking Project of Hebei (G2018037) and the Second Hospital of Hebei Medical University Foundation (2HC202128).

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Authors and Affiliations

  1. Department of Pathology, The Second Hospital of Hebei Medical University, 215 West Heping Road, Shijiazhuang, Hebei, 050017, People’s Republic of China

    Lei Lou, Manman Qin, Xiaoxi Tian, Wenli Guo & Yuehong Li

  2. School of Pharmacy, Hebei Medical University, 361 Zhongshan Eastern Road, Shijiazhuang, Hebei, 050017, People’s Republic of China

    Jiajun Li

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  1. Lei Lou
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Contributions

LL and YH conceived and designed the study; MM, XX, JJ, and WL performed developed methodology and wrote, reviewed, and revised the paper; LL, JJ and XX acquired, analyzed, and interpreted data and performed statistical analysis; JJ provided technical and material support. All authors read and approved the final paper.

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Correspondence to Yuehong Li.

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Lou, L., Li, J., Qin, M. et al. Correlation of MTAP immunohistochemical deficiency with CDKN2A homozygous deletion and clinicopathological features in pleomorphic xanthoastrocytoma. Brain Tumor Pathol 40, 15–25 (2023). https://doi.org/10.1007/s10014-022-00447-0

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