@article{3062661, title = "Caspase-3 immunohistochemical expression is a marker of apoptosis, increased grade and early recurrence in intracranial meningiomas", author = "Konstantinidou, A.E. and Givalos, N. and Gakiopoulou, H. and Korkolopoulou, P. and Kotsiakis, X. and Boviatsis, E. and Agrogiannis, G. and Mahera, H. and Patsouris, E.", journal = "Apoptosis", year = "2007", volume = "12", number = "4", pages = "695-705", issn = "1360-8185, 1573-675X", doi = "10.1007/s10495-006-0001-4", keywords = "androgen receptor; biological marker; caspase 3; cycline; DNA topoisomerase (ATP hydrolysing); estrogen; Ki 67 antigen; mitomycin C; monoclonal antibody; progesterone; protein bcl 2; single stranded DNA, adult; aged; apoptosis; article; disease course; disease free survival; enzyme analysis; enzyme degradation; enzyme release; female; histopathology; human; human cell; human tissue; immunohistochemistry; labeling index; major clinical study; male; meningioma; mitosis index; multivariate analysis; priority journal; prognosis; standard; statistical significance; tumor recurrence; univariate analysis, Aged; Animals; Apoptosis; Biological Markers; Caspase 3; Enzyme Precursors; Female; Humans; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Neoplasm Recurrence, Local; Receptors, Steroid; Survival Rate", abstract = "Caspase-3 is the ultimate executioner caspase that is essential for the nuclear changes associated with apoptosis. We investigated caspase-3 immunohistochemical expression in 58 primary intracranial meningiomas, using one monoclonal antibody detecting both precursor and cleaved caspase-3 (CPP32) and a second recognizing only the cleaved activated form (ASP175). Caspase-3 expression was analyzed in relation to baseline apoptosis-as illustrated by the expression of anti-single stranded DNA (ss-DNA), the antiapoptotic protein bcl-2, proliferation indices (Ki-67, PCNA, topoisomerase IIa, mitosin C), hormonal status (estrogen, progesterone, androgen receptors), standard clinicopathological parameters and patients' disease-free survival. Caspase-3 immunostaining was observed in 62% of cases for CPP32 and in 24% for ASP175. In both instances, the labeling index (LI) was significantly correlated with ss-DNA LI (p=0.038 and p=0.018). CPP32 but not ASP175 LI positively correlated with the mitotic index (p=0.001) and PCNA LI (p=0.004). Both CPP32 and ASP175 LIs were increased in nonbenign meningiomas (p<0.0001 and p=0.0035 respectively). In univariate and multivariate survival analyses, caspase-3 predicted meningioma recurrence, independently affecting disease-free survival (p=0.011 and p=0.047 respectively for CPP32; p<0.0001 and p=0.012 respectively for ASP175). Caspase-3 may prove to be a useful predictor of early recurrence in a group of neoplasms characterized by the frequent discordance between histology and clinical behavior. © 2006 Springer Science+Business Media, LLC." }