Immunohistochemical analysis of p53 and p21 in human primary glioblastomas in relation to proliferative potential and apoptosis.
The Cdk inhibitor p21/WAF1 can be transcriptionally activated by wild-type p53, not by mutant p53, and functions to block cell-cycle progression in many human neoplasms. We examined the immunohistochemical expression of p53 and p21 in 35 human primary glioblastomas in relation to tumor proliferation potential as assessed by the Ki-67 labeling index (LI) and the glioblastoma apoptosis index (AI). The expression of mutant p53 was observed in 74% of glioblastomas, wild-type p53 in 18% of glioblastomas, and p21 in 57% of glioblastomas. p21 expression was seen in 15 of 26 mutant p53-positive and 2 of 4 wild p53-positive tumors. Tumor Ki-67 LI correlated neither with p53 nor with p21 expression in glioblastomas. Apoptosis was identified in all 15 glioblastomas examined, with a mean (+/-SD) Al of 1.69+/-1.54, and correlated neither with p53 (wild or mutant) nor with p21 expression. The results of the present study suggest that p53 mutation and p21 protein expression are frequent in primary glioblastoma but lack correlation with tumor proliferation potential and apoptosis. The lack of correlation between p21 and p53 also suggests that p21 in glioblastomas may be induced by a p53-independent pathway.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D053938:DNA Fragmentation; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*