Diagnosis and Evaluation | Etiology and Pathogenesis > Tumor Progression

Proceedings of the AACR, Volume 44, 2nd ed., July 2003, Abstract No. 158 (Laboratory Investigation)

Meeting Abstract

Childrens Hospital Los Angeles, Univ. of Southern California, Los Angeles, CA; University of Maryland & University of Vienna, Baltimore, MD.

During the last decade, the aberrant expression of normal testicular proteins in neoplastically transformed cells became common knowledge. 
Cancer/testis-antigens (CTAs) represent a novel family of immunogenic proteins. 
This expression pattern might contribute to the genetic instability of neoplastically transformed cells. 
In normal adult tissues, most 23 human MAGE genes are expressed only in the testis, but only in the mitotic spermatogonia (germ cells) and in the primary spermatocytes. 
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 (IC) antigen detection techniques to search for evidence of abnormal p53 protein and MAGE-1 expression in 10 human childhood astrocytoma (ASTR) subtypes (five pilocytic, two anaplastic, one anaplastic ASTR with primitive neuroectodermal tumor elements, one ASTR containing a majority of oligodendrocytes and one glioblastoma multiforme). 
The IC was carried out on routine, formalin fixed, paraffin-wax embedded 3 to 4 µm thick ASTR tissue sections. 
An enzyme conjugated four step, indirect, biotin-streptavidin based method was employed. 
Presence and cellular localization of the MAGE-1, was observed only in anaplastic, high grade ASTRs (100%), including glioblastomas. 
Surprisingly, p53 protein expression was demonstrated in all ten ASTRs. 
The immunoreactivity pattern was heterogeneous, with cell 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. 
MAGE-1 expression in the lowest grade, pilocytic ASTRs was never identified. 
The MAGE-1 and p53 expression levels may also be used to evaluate the malignant and dedifferentiation tendencies of low grade ASTRs and predicting the likelihood of mutations of the genome and further dedifferentiation towards even more malignant anaplastic ASTR and glioblastoma multiforme IPs.
The expression of MAGE-1 is similar to a green light giving the go ahead for the future development of individualized ASTR vaccines in brain tumor immunotherapy.

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