p53 accumulation and apoptosis in embolized meningiomas.
Preoperative embolization of meningiomas is performed to decrease blood loss at surgery. While it is also expected to reduce tumor recurrence by producing necrosis at the site of dural attachment, very little has been described about what happens to the non-necrotic tumor cells. We investigated how the proliferative activities of meningiomas were modified after embolization. In nine meningiomas which were embolized preoperatively, proliferative potentials and expression of cell cycle inhibitors were assessed immunohistochemically using MIB-1, anti-53 (DO-1 and DO-7), and anti-p21 (WAF1/CIP1) monoclonal antibodies. To determine whether a cell underwent apoptotic death besides necrosis, we applied the terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling method. Results were compared with control meningiomas without embolization. MIB-1 positive cells often gathered in perinecrotic areas, although the mean MIB-1 staining index of the embolized meningiomas was not significantly different from the control. p53 and its downstream effector p21 accumulated mainly in the perinecrotic areas in eight of the nine embolized meningiomas. Apoptosis was also observed in the concomitant areas. Double staining for both MIB-1 and p21 frequently showed positive cells for both antibodies. The accumulation of MIB-1 positive cells in the embolized meningiomas may not be a sign of fast growth or malignancy, but it may implicate arrest of cell cycle by the p21. This study indicates that embolized meningiomas exhibit not only necrosis but also apoptosis and cell cycle arrest. The latter effects appear to be at least partly p53 dependent.
Nakasu
S
S
Department of Neurosurgery, Shiga University of Medical Science, Japan.
Nakajima
M
M
Nakazawa
T
T
Nakasu
Y
Y
Handa
J
J
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000737:chemistry; D017209:Apoptosis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004249:DNA Damage; D004253:DNA Nucleotidylexotransferase; D005260:Female; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D008579:Meningioma / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D008940:Mitotic Index; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D013194:Staining and Labeling; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000911:Antibodies, Monoclonal; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D004253:DNA Nucleotidylexotransferase