p16(INK4a) and p19(INK4d) mRNA expression in neuroglial tumours: correlation with Ki67 proliferation index

The INK4a-ARF locus encodes two unrelated proteins that both function in tu mour suppression: p16(INK4a) and p19(INK4d). Although p19(INK4d) expression has not been studied in central nervous system (CNS) tumours, it has been reported that p16(INK4a) inactivation is involved in the growth of glioblas tomas. This observation has not been reported in relation to other CNS tumo urs. To understand further the role of p16(INK4a) and p19(INK4d) in neurogl ial tumour growth, expression of both p16(INK4a) and p19(INK4d) mRNAs was s tudied by reverse transcription polymerase chain reaction RT-PCR in 59 neur oglial tumours, in which Ki67 labelling indices (LI) were also determined. p16(INK4a) 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 ependymo mas and 3/3 anaplastic ependymomas but not in normal brain. In contrast, p1 9(INK4d) mRNA was detected in all tumours and control tissues. p16(INK4a) e xpression was associated with a low Ki67 LT in glioblastomas but not in oth er tumours. p16(INK4a) expression was not related to anaplasia in oligodend rogliomas and ependymomas. In tumours expressing p16(INK4a), in situ hybrid ization showed a widespread expression of p16(INK4a) mRNA in tumour cells a nd in foci of microvascular proliferation, These results strongly support t he concept that p16(INK4a) is involved in the regulation of proliferation i n glioblastomas. Other cell cycle regulators which are yet unknown may also pray a role in the control of oligodendrogliomas or ependymomas outgrowth. Further studies are required to evaluate the role of p19(INK4d) in neurogl ial tumours.