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

Apoptosis. 2007 Apr;12(4):695-705. doi: 10.1007/s10495-006-0001-4. Epub 2006 Dec 5.


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.

MeSH terms

  • Aged
  • Animals
  • Apoptosis / physiology*
  • Biomarkers / metabolism*
  • Caspase 3 / metabolism*
  • Enzyme Precursors / metabolism
  • Female
  • Humans
  • Male
  • Meningeal Neoplasms* / metabolism
  • Meningeal Neoplasms* / pathology
  • Meningioma* / metabolism
  • Meningioma* / pathology
  • Middle Aged
  • Neoplasm Recurrence, Local*
  • Receptors, Steroid / metabolism
  • Survival Rate


  • Biomarkers
  • Enzyme Precursors
  • Receptors, Steroid
  • Caspase 3