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p16INK4a and p19INK4d mRNA expression in neuroglial tumours: correlation with Ki67 proliferation index
C Bouvier-Labit1, M Civatte, C Bartoli
1Laboratoire de Biopathologie Nerveuse et Musculaire, Faculté de Médecine, Marseille, France.
Abstract:
The INK4a-ARF locus encodes two unrelated proteins that both function in tumour suppression: p16INK4a and p19INK4d. Although p19INK4d expression has not been studied in central nervous system (CNS) tumours, it has been reported that p16INK4a inactivation is involved in the growth of glioblastomas. This observation has not been reported in relation to other CNS tumours. To understand further the role of p16INK4a and p19INK4d in neuroglial tumour growth, expression of both p16INK4a and p19INK4d mRNAs was studied by reverse transcription polymerase chain reaction RT-PCR in 59 neuroglial tumours, in which Ki67 labelling indices (LI) were also determined. P16INK4a mRNA was found in all pilocytic astrocytomas (7/7), in all grade II and III astrocytomas (7/7 and 4/4, respectively), in 4/12 glioblastomas, 8/8 oligodendrogliomas, 10/11 anaplastic oligodendrogliomas, 4/7 ependymomas and 3/3 anaplastic ependymomas but not in normal brain. In contrast, p19INK4d mRNA was detected in all tumours and control tissues. p16INK4a expression was associated with a low Ki67 LI in glioblastomas but not in other tumours. P16INK4a expression was not related to anaplasia in oligodendrogliomas and ependymomas. In tumours expressing p16INK4a, in situ hybridization showed a widespread expression of p16INK4a mRNA in tumour cells and in foci of microvascular proliferation. These results strongly support the concept that p16INK4a is involved in the regulation of proliferation in glioblastomas. Other cell cycle regulators which are yet unknown may also play a role in the control of oligodendrogliomas or ependymomas outgrowth. Further studies are required to evaluate the role of p19INK4d in neuroglial tumours.
Insights
The study investigated p16INK4a and p19INK4d in neuroglial tumors. P16INK4a expression correlated with lower proliferation in glioblastomas, suggesting its role in tumor growth regulation.
Area of Science:
- Oncology
- Molecular Biology
- Neuroscience
Background:
- The INK4a-ARF locus yields tumor suppressors p16INK4a and p19INK4d.
- p16INK4a inactivation is linked to glioblastoma growth, but its role in other CNS tumors is unclear.
- p19INK4d expression in CNS tumors remains uninvestigated.
Purpose of the Study:
- To investigate the expression of p16INK4a and p19INK4d mRNAs in various neuroglial tumors.
- To correlate p16INK4a and p19INK4d expression with tumor proliferation markers (Ki67 LI).
- To elucidate the role of these proteins in the pathogenesis of neuroglial tumors.
Main Methods:
- Reverse transcription polymerase chain reaction (RT-PCR) was used to detect p16INK4a and p19INK4d mRNA.
- Ki67 labelling index (LI) was determined to assess tumor cell proliferation.
- In situ hybridization was employed to localize p16INK4a mRNA expression.
Main Results:
- p16INK4a mRNA was detected in most neuroglial tumors but not in normal brain tissue.
- p19INK4d mRNA was ubiquitously expressed in both tumors and control tissues.
- p16INK4a expression correlated with a lower Ki67 LI in glioblastomas, indicating a role in proliferation control.
Conclusions:
- p16INK4a plays a significant role in regulating proliferation in glioblastomas.
- The roles of p16INK4a and p19INK4d in other neuroglial tumors, such as oligodendrogliomas and ependymomas, require further investigation.
- Unknown cell cycle regulators may influence the growth of oligodendrogliomas and ependymomas.