title: Caspase-3 immunohistochemical expression is a marker of apoptosis, increased grade and early recurrence in intracranial meningiomas.
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.
authors.affiliation: Department of Pathology, Medical Faculty, National Kapodistrian University of Athens, Athens, Greece. ankon@med.uoa.gr
authors.forename: A E
authors.initials: AE
authors.lastname: Konstantinidou
authors.forename: N
authors.initials: N
authors.lastname: Givalos
authors.forename: H
authors.initials: H
authors.lastname: Gakiopoulou
authors.forename: P
authors.initials: P
authors.lastname: Korkolopoulou
authors.forename: X
authors.initials: X
authors.lastname: Kotsiakis
authors.forename: E
authors.initials: E
authors.lastname: Boviatsis
authors.forename: G
authors.initials: G
authors.lastname: Agrogiannis
authors.forename: H
authors.initials: H
authors.lastname: Mahera
authors.forename: E
authors.initials: E
authors.lastname: Patsouris
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D004792:Enzyme Precursors / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000378:metabolism / Q000473:pathology; D008579:Meningioma / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011987:Receptors, Steroid / Q000378:metabolism; D015996:Survival Rate
chemical_list: D015415:Biomarkers; D004792:Enzyme Precursors; D011987:Receptors, Steroid; D053148:Caspase 3