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KMID : 0350519950480030855
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Journal of Catholic Medical College
1995 Volume.48 No. 3 p.855 ~ p.865
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Aberrant Expression of p53 , MDM2 Protein and Prolifer ative Activity in Glioma
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Abstract
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Different molecular mechanisms have been implicated in the malignant transformation of glial cells and the progression of gliomas. These include amplification and enhanced expression of certain cellular oncogenes as well as inactivation of tumor
suppessor genes by mutation or deletion. In gliomas, the most frequently studied tumor suppressor gene is the p53 eene which has been found to be mutated in a considerable fraction of astrocytomas and glioblastomas. Mutations that alter the
function of
the p53 gene product are thought to play a critical role in glial tumorigenesis. The murine double minute 2 (MDM2) gene has been shown to code for a cellular protein that forms a conplex with the p53 tumor supperessor gene product and inhibits
its
function. The fact that MDM2 can negatively regulate p53 suggests MDM2 could function as an oncogene when overexpressed.
We investigated the expression of p53, MDM2 and proliferative activity of the tumor cels in 71 cases of glioma (17 cases of differentiated astrocytoma, 25 cases of anaplastic astrocytoma and 29 cases of glioblastoma). Their paraffin-embedded
tissue
sections were immunostained with monoclonal antibody (p53 and PCNA, proliferating cell nuclear antigen) and polyclonal antibody (MDM2) for detection of p53, MDM2 and PCNA retrospectively.
@ES The results were as follows :
@EN 1. The p53 staining was positive in 28 cases (39.4%) and MDM2 staining in 5 cases (7.0%) of 71 gliomas.
2. The p53 positive-staining was detected in 2 cases (11.8%) of 17 differentiated astrocytomas (gradeⅡ), 9 cases (36.0%) of 25 anaplastic astrocytomas (gradeⅢ) and 17 cases (58.6%) of 29 glioblastomas (gradeⅣ). The p53 expression was
associated
with
malignancy grade (P<0.005) and proliferative activity was strongly associated with malignancy grade (P=0.0001).
3. The p53-negative tumors (40.6±10.1% versus 19.6±15.0%) (P=0.0001). But, MDM2 expression was not associated with proliferative activity (P=0.4575).
4. The proportion of p53 immunoreactivity had significant association with proliferative activity : the more the proportion of p53 immunoreactivity increased, the higher PCNA-labeling index elevated (P=0.0001).
5. None of the tumors with MDM2 expression showed immunorectivity for p53.
These results suggest that the mutation of p53 gene plays a critical role in malignant transformation in glioma and it could be the prognostic factor for histologically same grade gliomas, and that a subset of human gliomas escapes from
p53-regulated
growth control by amplification and overexpression of MDM2. Therefore, gene study targeting these genes may be useful for the managenment of human glioma as a diagnostic modality.
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