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p16 INK 4a and p19 INK 4d mRNA expression in neuroglial tumours: correlation with Ki67 proliferation index
Author(s) -
C BouvierLabit,
M. Civatte,
Catherine Bartoli,
Wanda Renaud,
Pellissier Jf,
Dominique FigarellaBranger
Publication year - 1999
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1046/j.1365-2990.1999.00203.x
Subject(s) - biology , in situ hybridization , pathology , anaplasia , immunohistochemistry , proliferation index , cancer research , reverse transcription polymerase chain reaction , messenger rna , medicine , immunology , gene , biochemistry
The INK4a‐ARF locus encodes two unrelated proteins that both function in tumour 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 glioblastomas. This observation has not been reported in relation to other CNS tumours. To understand further the role of p16 INK4a and p19 INK4d in neuroglial tumour growth, expression of both p16 INK4a and p19 INK4d mRNAs was studied by reverse transcription polymerase chain reaction RT‐PCR in 59 neuroglial 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 ependymomas and 3/3 anaplastic ependymomas but not in normal brain. In contrast, p19 INK4d mRNA was detected in all tumours and control tissues. p16 INK4a expression was associated with a low Ki67 LI in glioblastomas but not in other tumours. P16 INK4a expression was not related to anaplasia in oligodendrogliomas and ependymomas. In tumours expressing p16 INK4a , in situ hybridization showed a widespread expression of p16 INK4a mRNA in tumour cells and in foci of microvascular proliferation. These results strongly support the concept that p16 INK4a 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 p19 INK4d in neuroglial tumours.