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

Konstantinidou, A. E.; Givalos, N.; Gakiopoulou, Hara; Korkolopoulou, Penelope; Kotsiakis, Xenophon; Boviatsis, Efstathios; Agrogiannis, George; Mahera, H; Patsouris, Efstratios

doi:10.1007/s10495-006-0001-4

Cited by 64 publications

(52 citation statements)

References 39 publications

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“…In meningioma samples analysed a higher number of TUNEL-positive cells and a different amount of apoptotic signals have been detected compared to that observed by other authors [6,27]. Moreover a low amount of caspase-3 active form expression has been scored in grade II and III meningiomas.…”

Section: Discussionmentioning

confidence: 62%

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Signals of Apoptotic Pathways in Several Types of Meningioma

Sabbatini

Comi

Chiocchetti

et al. 2010

Pathol. Oncol. Res.

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Meningiomas are intracranial tumour derived from meningothelial cells, which aggressive behaviour has been frequently associated to cell apoptosis. In this paper activation of several factors involved in apoptosis has been investigated on biopsies of primary, non recurrent meningiomas. Benign (meningotheliomatous, transitional, fibrous, angiomatous), atypical and anaplastic meningiomas were analysed by immunohistochemistry and western blot, to visualize the occurring of different apoptotic pathways and their association with clinical grading. Apoptotic cell have been detected by a double colorimetric staining for TUNEL and caspase-3 active form. Apoptotic signal positive cells have been detected in all type of meningiomas analysed, with exception of meningotheliomatous meningiomas. Differences have been found in the activation of apoptotic pathways between several types of grade I meningiomas and among benign, anaplastic and atypical meningiomas. An intense expression of several apoptotic inhibitor occurred in grade I meningiomas. The correlation among expression of apoptotic and inhibitory factors and cell proliferation index may suggest that in grade I meningiomas apoptosis may be related to mechanisms involved into tumor cells surviving. Instead in grade II and III meningiomas the same correlation seems indicate an high turnover of tumor cells that might be useful as index of cell proliferation and tumor mass growth.

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Section: Discussionmentioning

confidence: 62%

“…In fact a malfunction of the apoptotic pathways leads to the setting of malignant tumors [3,4]. Presence of apoptosis has been frequently associated to recurrence and/or aggressive behaviour of meningiomas [5,6].…”

Section: Introductionmentioning

confidence: 99%

Signals of Apoptotic Pathways in Several Types of Meningioma

Sabbatini

Comi

Chiocchetti

et al. 2010

Pathol. Oncol. Res.

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“…The activation of effectors caspases, like caspase-3, is an event also known as "point of no return" of apoptosis, beyond which the cells certainly will entry to apoptosis (Asselin et al 2001). The presence of CC3 has been demonstrated in many neoplasms, such as breast cancer, gliomas, neuroblastomas and sarcomas (Konstantinidou et al 2007, Kobayashi et al 2007, Matsubara et al 2008, Nassar et al 2008. Double inactivation of NF1 gene in Schwann cells seems to be the common event in neurofibromas and MPNSTs.…”

Section: Disease Free Survivalmentioning

confidence: 99%

“…In some tumors, i.e. meningiomas (Konstantinidou et al 2007), and Burkitt's and Burkitt-like lymphomas (Nomura et al 2008), the location of caspase-3 protein has been shown to be a prognostic marker. In a study with 41 sarcomas, but none MPNSTs, the overall and disease free survival were lower in cases of patients with higher levels of CC3 (Matsubara et al 2008).…”

Section: Disease Free Survivalmentioning

confidence: 99%

Evaluation of Bcl-2, Bcl-x and Cleaved Caspase-3 in Malignant Peripheral Nerve Sheath Tumors and Neurofibromas

Cunha

Caruso²,

Faria³

et al. 2013

An. Acad. Bras. Ciênc.

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AIMS:To study the expression of Bcl-2, Bcl-x, as well the presence of cleaved caspase-3 in neurofibromas and malignant peripheral nerve sheath tumors. The expression of Bcl-2 and Bcl-x and the presence of cleaved caspase 3 were compared to clinicopathological features of malignant peripheral nerve sheath tumors and their impact on survival rates were also investigated. MATERIALS AND METHODS: The evaluation of Bcl-2, Bcl-x and cleaved caspase-3 was performed by immunohistochemistry using tissue microarrays in 28 malignant peripheral nerve sheath tumors and 38 neurofibromas. Immunoquantification was performed by computerized digital image analysis. CONCLUSIONS: Apoptosis is altered in neurofibromas and mainly in malignant peripheral nerve sheath tumors. High levels of cleaved caspase-3 are more common in tumors with more aggressive histological features and it is associated with lower disease free survival of patients with malignant peripheral nerve sheath tumors.

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“…ISSN 2472-1158 that a high expression of CASP3 has been found associated with recurrence in meningioma [19,20], which might be due to the use of a fresh specimen instead of archival ones and inclusion of all the grade of meningiomas.…”

Section: Journal Of Clinical Epigeneticsmentioning

confidence: 99%

Dysregulation of Apoptosis Caused by Aberrant Histone Modification Influences on the Recurrence of Meningiomas

Kim¹

2017

J Clin Epigenet

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Background: Alteration of apoptosis is related with progression and recurrence of atypical meningiomas (AMs). However, no comprehensive study has been conducted regarding histone modification regulating apoptosis in AMs. This study was aimed to determine the prognostic values of certain apoptosis-associated factors, and examine the role of histone modification on apoptosis in AMs. Materials and method:The medical records of 67 patients with AMs, as diagnosed during recent 13 years, were reviewed retrospectively. Immunohistochemical staining was performed on archived paraffin-embedded tissues for pro-apoptotic factors (CASP3, IGFBP, TRAIL-R1, BAX, and XAF1), anti-apoptotic factors (survivin, ERK, RAF1, MDM2, and BCL2), and the histone modifying enzymes (MLL2, RIZ, EZH1, NSD2, KDM5c, JMJD2a, UTX, and JMJD5).Results: Twenty-six (38.8%) patients recurred during the follow-up period (mean duration 47.7 months). In terms of time-to-recurrence (TTR), overexpression of CASP3, TRAIL-R1, and BAX had a longer TTR than underexpression, and overexpression of Survivin, MDM2, and BCL2 had a shorter TTR than underexpression (P<0.05). Additionally, overexpression of MLL2, UTX, and JMJ5 had shorter TTRs than underexpression, and overexpression of KDM5c had a longer TTR than underexpression. However, in the multi-variate analysis of predicting factors for recurrence, underexpression of CASP3 (P<0.001), and BAX (P<0.001), and overexpression of survivin (P=0.007), and MDM2 (P=0.037) were associated with recurrence independently, but any enzymes modifying histone were not associated with recurrence. Conclusion:This study suggests certain apoptosis-associated factors should be associated with recurrence of AMs, which may be regulated epigenetically by histone modifying enzymes.Keywords: Atypical meningioma; Apoptosis; Histone modification; Recurrence; Epigenetics a low recurrence rate after gross total resection (GTR) [5,6]. series have included only a few patients [9,10]. Even after GTR, tumor recurrence is observed after several years in some 20 to 30% of cases [11,12]. Thus, a reasonable organized therapeutic strategy could be instituted if recurrence could be predicted from surgical specimens, and for this reason many authors have investigated the histological indices of proliferative and apoptotic potential in resected AMs, such as, BCL2 [13,14], proliferating cell nuclear antigen [13], and Ki-67 cell cycle-specific nuclear antigen [15,16]. From these indices, researchers have attempted to establish the nature of the relationship between histological aggressiveness and the recurrence of AMs.

show abstract

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

Cited by 64 publications

References 39 publications

Signals of Apoptotic Pathways in Several Types of Meningioma

Signals of Apoptotic Pathways in Several Types of Meningioma

Evaluation of Bcl-2, Bcl-x and Cleaved Caspase-3 in Malignant Peripheral Nerve Sheath Tumors and Neurofibromas

Dysregulation of Apoptosis Caused by Aberrant Histone Modification Influences on the Recurrence of Meningiomas

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