IMMUNOHISTOCHEMICAL DETECTION OF P53 PROTEIN EXPRESSION IN VARIOUS CHILDHOOD ASTROCYTOMA SUBTYPES - SIGNIFICANCE IN TUMOR PROGRESSION

Detection of p53 protein expression and overexpression has been report ed to be associated with poor prognosis in a number of human malignanc ies. The aim of this study was to utilize immunocytochemical antigen d etection techniques to search for evidence of abnormal p53 protein acc umulation in ten human childhood astrocytoma (ASTR) subtypes (five pil ocytic, two pure anaplastic, one anaplastic ASTR with primitive neuroe ctodermal armor elements, one ASTR containing a majority of oligodendr ocytes and one glioblastoma multiforme). The immunocytochemistry was c arried out on routine, formalin fixed, paraffin-wax embedded 3 to 4 mu m thick ASTR tissue sections. A four step, indirect, biotin-streptavi din based method was employed with peroxidase enzyme conjugation. Surp risingly, p53 protein expression was demonstrated in all ten ASTRs. Th e 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 mul tiforme. Low-grade human ASTRs possess an intrinsic tendency for cell dedifferentiation toward the embryonic cell immunophenotype (IF). Loss of p53 function is associated with most, if not all, human malignanci es. 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 b e involved in the early stages of ASTR progression fram the grade I pi locytic subtype to the more ''malignant'' pure ASTR, which is characte rized by p53 gene mutations. The loss of p53 provides the necessary ge netic instability needed for fur ther IP changes and further progressi on towards more malignant IPs, e.g. anaplastic ASTR and glioblastoma m ultiforme. Such facts make the use of p53 in the assessment of ASTRs i ndispensible. p53 levels may be used in identifying cell clones within pilocytic ASTR microenvironments, which have a clear tendency for pro gression toward more malignant IPs and the establishment of the altera tion of the p53 gene in more advanced ASTR subtypes (grades II to IV).