Immunohistochemical detection of p53 protein expression in various childhood astrocytoma subtypes: significance in tumor progression.
Detection of p53 protein expression and overexpression has been reported to be associated with poor prognosis in a number of human malignancies. The aim of this study was to utilize immunocytochemical antigen detection techniques to search for evidence of abnormal p53 protein accumulation in ten human childhood astrocytoma (ASTR) subtypes (five pilocytic, two pure anaplastic, one anaplastic ASTR with primitive neuroectodermal tumor elements, one ASTR containing a majority of oligodendrocytes and one glioblastoma multiforme). The immunocytochemistry was carried out on routine, formalin fixed, paraffin-wax embedded 3 to 4 microns thick ASTR tissue sections. A four step, indirect, biotin-streptavidin based method was employed with peroxidase enzyme conjugation. Surprisingly, p53 protein expression was demonstrated in all ten ASTRs. The immunoreactivity pattern was mostly heterogeneous, with cells groups of similar intensity clustered within the ASTRs. The number of cells stained and the intensity of the immunoreactivity correlated directly with the known degree of malignancy of the various subtypes of ASTRs: lowest in the pilocytic ASTR cases and highest in the glioblastoma multiforme. Low-grade human ASTRs possess an intrinsic tendency for cell dedifferentiation toward the embryonic cell immunophenotype (IP). Loss of p53 function is associated with most, if not all, human malignancies. Mutation of p53 has yet to be demonstrated in pilocytic ASTRs. The accumulation of p53 in some pilocytic ASTR cells, as demonstrated in our study, suggests that the mere dysfunction of the p53 protein may be involved in the ealry stages of ASTR progression from the grade I pilocytic subtype to the more "malignant" pure ASTR, which is characterized by p53 gene mutations. The loss of p53 provides the necessary genetic instability needed for further IP changes and further progression towards more malignant IPs, e.g. anaplastic ASTR and glioblastoma multiforme. Such facts make the use of p53 in the assessment of ASTRs indispensible. p53 levels may be used in identifying cell clones within pilocytic ASTR microenvironments, which have a clear tendency for progression toward more malignant IPs and the establishment of the alteration of the p53 gene in more advanced ASTR subtypes (grades II to IV).
Bodey
B
B
Department of Pathology, School of Medicine, University of Southern California, Los Angeles, USA.
Gröger
A M
AM
Bodey
B
B
Siegel
S E
SE
Kaiser
H E
HE
D000818:Animals; D001254:Astrocytoma / Q000737:chemistry* / Q000473:pathology; D002648:Child; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D009154:Mutation; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D016159:Tumor Suppressor Protein p53