Caspase-3 immunohistochemical expression is a marker of apoptosis,increased grade and early recurrence in intracranial meningiomas |
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Authors: | A E Konstantinidou N Givalos H Gakiopoulou P Korkolopoulou X Kotsiakis E Boviatsis G Agrogiannis H Mahera E Patsouris |
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Institution: | (1) Department of Pathology, Medical Faculty, National Kapodistrian University of Athens, Athens, Greece;(2) Department of Neurosurgery, General Hospital of Hania, Creta, Greece;(3) Department of Neurosurgery, “Evangelismos” Hospital, Athens, Greece;(4) Laboratory of Pathology, “KAT” General Hospital, Athens, Greece |
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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. |
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Keywords: | Meningioma Active caspase-3 CPP32 ASP175 ss-DNA bcl-2 Ki-67 PCNA Topoisomerase IIa Mitosin C Apoptosis Proliferation Recurrence Prognosis Disease-free survival |
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