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Caspase-3 immunohistochemical expression is a marker of apoptosis, increased grade and early recurrence in intracranial meningiomas

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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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Authors and Affiliations

  1. Department of Pathology, Medical Faculty, National Kapodistrian University of Athens, Athens, Greece

    A. E. Konstantinidou, N. Givalos, H. Gakiopoulou, P. Korkolopoulou, G. Agrogiannis & E. Patsouris

  2. Department of Neurosurgery, General Hospital of Hania, Creta, Greece

    X. Kotsiakis

  3. Department of Neurosurgery, “Evangelismos” Hospital, Athens, Greece

    E. Boviatsis

  4. Laboratory of Pathology, “KAT” General Hospital, Athens, Greece

    H. Mahera

Authors
  1. A. E. Konstantinidou
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  2. N. Givalos
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  3. H. Gakiopoulou
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  4. P. Korkolopoulou
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  5. X. Kotsiakis
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  6. E. Boviatsis
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  7. G. Agrogiannis
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  8. H. Mahera
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  9. E. Patsouris
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Correspondence to A. E. Konstantinidou.

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Konstantinidou, A.E., Givalos, N., Gakiopoulou, H. et al. Caspase-3 immunohistochemical expression is a marker of apoptosis, increased grade and early recurrence in intracranial meningiomas. Apoptosis 12, 695–705 (2007). https://doi.org/10.1007/s10495-006-0001-4

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  • DOI: https://doi.org/10.1007/s10495-006-0001-4

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