[Expression of P21 WAF1/CIP1 in human astrocytomas in correlating with P53, MDM2, and cellular proliferation index].
OBJECTIVE
To study the correlation between the expression of p21, p53, MDM2 gene products and the initiation and progression of human astrocytomas.


METHODS
The expression of P21, P53, MDM2, and proliferative cell nuclear antigen (PCNA) labeling index using immunohistochemistry in 41 paraffin embedded human astrocytoma samples. As well as the expression of p21 mRNA using mRNA in situ hybridization in 24 fresh human astrocytoma samples stored at -70 degrees C were investigated. In immunohistochemistry, we divided whole tumor cells by positive tumor cell nuclei to obtain labeling index (LI), in this way we could understand the protein product expression of gene in astrocytoma in different patients. In mRNA in situ hybridization, the expression of p21 mRNA was scored according to the rough percentage of positive cells.


RESULTS
In p21 mRNA in situ hybridization, the positive staining was present in 87.5%. In immunohistochemistry, positive P21, P53, MDM2, and PCNA staining were presented in 75.6%, 68.3%, 65.9%, 100% respectively. Higher levels of P21 protein expression were seen in higher histological grade (P = 0.001). The association between P21 expression positively correlated with proliferation index. But not with P53 expression and MDM2 expression. The association between P53 expression and proliferation indices were statistically significant, but the expression of P53 was not related to tumor grade. There was no association between MDM2 expression and grade, or cellular proliferation index. Linear stepwise regression analysis showed the parameters affecting tumor grade were PCNA LI (P = 0.000) and P21 LI (P = 0.001).


CONCLUSIONS
(1) Both p21 mRNA and P21 protein were overexpressed in human astrocytomas, the overexpression was related to cellular proliferation index, but was not related to P53 expression, suggesting there could be P53-independent pathway to induce the P21 expression, in addition, the overexpression of P21 alone appeared insufficient to suppress tumor growth, provided the participation of PCNA. (2) The expression of P53 protein was associated with proliferation indices, but was not with the tumor malignancy, this indicated that the inactivation of P53 might be the early event in the growth of human astrocytomas. (3) P21 labeling index and cellular proliferation index influenced the tumor histological grade, our data indicated that p21 gene might play a role in the progression of human astrocytomas.
Xu
Q Z
QZ
Department of Pathology, Xuan Wu Hospital, Capital University of Medical Sciences, Beijing 100053, China.
Liu
F
F
Lu
D H
DH
Yu
S Z
SZ
Yang
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D051736:Proto-Oncogene Proteins c-mdm2; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2