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CDKN2/p16 inactivation and p16 immunohistochemistry in astrocytic gliomas
R Piva1, P Cavalla, S Bortolotto
1Department of Neuroscience, University of Turin, via Cherasco, 15 I-10126 Turin, Italy.
Abstract:
CDKN2/p16 inactivation is the most frequent alteration in the molecular regulation of G1-S transition. CDKN2/p16 homozygous deletions was studied in paraffin-embedded sections of 45 astrocytic tumours by multiplex PCR. Immunohistochemistry for p16 and proliferation marker Ki-67 MIB-1 was performed in adjacent sections; their labelling index (LI) have been calculated. CDKN2/p16 gene was not deleted in astrocytomas, while homozygous deletion was found in 26.7% anaplastic astrocytomas, and in 55.0% of glioblastomas. Analysis of CDKN2/p16 homozygous deletion in discrete areas of the same tumour, showed that the deletion occurred independently of the phenotypic aspect of the areas. Nevertheless a genotypic and phenotypic heterogeneity is present in few cases. p16 immunohistochemistry mostly corresponds to the genotypic pattern. No correlation was found between CDKN2/p16 homozygous deletion and MIB-1 LI.
Insights
CDKN2/p16 gene deletions are common in aggressive brain tumors like glioblastomas, but not in lower-grade astrocytomas. This genetic alteration did not correlate with tumor cell proliferation (MIB-1 LI).
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Genetics
Background:
- CDKN2/p16 inactivation is a frequent event in G1-S cell cycle regulation.
- Understanding its role in astrocytic tumors is crucial for molecular classification and targeted therapies.
Purpose of the Study:
- To investigate the frequency of CDKN2/p16 homozygous deletions in various grades of astrocytic tumors.
- To correlate these genetic alterations with tumor phenotype and proliferation markers.
Main Methods:
- Analysis of 45 astrocytic tumors using multiplex PCR for CDKN2/p16 homozygous deletions.
- Immunohistochemistry for p16 protein and Ki-67 (MIB-1) proliferation marker on adjacent tissue sections.
Main Results:
- CDKN2/p16 gene deletions were absent in astrocytomas.
- Homozygous deletions were detected in 26.7% of anaplastic astrocytomas and 55.0% of glioblastomas.
- p16 immunohistochemistry generally mirrored the genetic deletion status, with some cases showing heterogeneity. No correlation was found between CDKN2/p16 deletion and MIB-1 labeling index.
Conclusions:
- CDKN2/p16 homozygous deletion is a significant molecular event distinguishing high-grade astrocytomas (glioblastomas) from lower-grade tumors.
- The genetic status of CDKN2/p16 largely aligns with p16 protein expression, but tumor heterogeneity exists.
- CDKN2/p16 deletion status does not appear to directly influence the proliferation rate as measured by MIB-1 LI in these tumors.