Malignant astrocytomas with homozygous CDKN2/p16 gene deletions have higher Ki-67 proliferation indices

Yasuhiro Ono, Takashi Tamiya, Tomotsugu Ichikawa, Katsuzou Kunishio, Kengo Matsumoto, Tomohisa Furuta, Takashi Ohmoto, Keisuke Ueki, David N. Louis

Research output: Contribution to journalArticlepeer-review

85 Citations (Scopus)

Abstract

p16 is involved in a cell cycle regulatory cascade that includes cyclin- dependent kinase 4 (cdk4), cyclin DI and pRb. Alterations of each of these components have been described in primary human glioblastoma multiforme (GBM) or GBM cell lines, and alterations of the individual components of this pathway appear inversely correlated with one another. While this suggests that disruption of any individual component has similar oncogenic effects, homozygous deletions of the CDKN2/p16 gene are the most common genetic alteration. We investigated the relationship between homozygous CDKN2/p16 deletions and cellular proliferation in 50 primary astrocytomas (2 WHO grade I pilocytic astrocytoma. 15 grade II astrocytomas, 20 grade III anaplastic astrocytomas and 13 grade IV GBMs). Using a comparative multiplex PCR assay, homozygous deletions of the CDKN2/p16 gene were detected in 5 anaplastic astrocytomas (25% and 6 GBMs (46%), but in none of the lower-grade tumors. Ki-67 immunohistochemistry was used to assess the number of proliferating cells in the same samples used for molecular genetic analysis. In both anaplastic astrocytomas and GBMs, Ki-67 proliferation indices were significantly higher in tumors with CDKN2/p16 deletions (20%t than in those without deletions (1()%; p=0.000l). These results suggest that homozygous CDKN2/p16 deletions in high grade astrocytomas may have a more deleterious effect on cell cycle control than the other aberrations in the p16-cdk4- cyclin D1-pRb pathway, and may provide one explanation for why homozygous CDKN2/p16 deletions are more common genetic events in high-grade astrocytomas than RB mutations or CDK4 amplification.

Original languageEnglish
Pages (from-to)1026-1031
Number of pages6
JournalJournal of Neuropathology and Experimental Neurology
Volume55
Issue number10
DOIs
Publication statusPublished - Oct 1996

Keywords

  • Astrocytoma
  • CDKN2
  • Cell cycle
  • Ki-67
  • p16

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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