DNA topoisomerase IIα expression correlates with cell proliferation but not with recurrence in intracranial meningiomas

Konstantinidou, A. E.; Patsouris, Efstratios; Korkolopoulou, Penelope; Kavantzas, Nikolaos; Mahera, H; Davaris, P

doi:10.1046/j.1365-2559.2001.01229.x

Cited by 17 publications

(14 citation statements)

References 26 publications

(39 reference statements)

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“…However, heterogenicity of cell populations and features secondary to technical manipulation which may mask the mitotic figures, 7,46 render proliferation markers for quantitative assessment of the biological behavior of meningiomas necessary. [2][3][4][5][6][7][8][9][10] Numerous studies have shown that immunohistochemistry of the nonhistone nuclear protein Ki-67, expressed in the G 1 , S, G 2 , and M phases of the cell cycle, may be the simplest and most reliable means of estimating growth fractions in various brain tumors including meningiomas. [2][3][4][5][6][7][8][47][48][49] The monoclonal MIB-1 antibody detects recombinant Ki-67 antigen, 11,12 but unlike previ- ously available Ki-67 antibodies, MIB-1 can be used on formalin fixed, paraffin-embedded tissue as it detects a fixation and embedding resistant epitope on the Ki-67 antigen in sections previously microwaved in a citrate buffer.…”

Section: Discussionmentioning

confidence: 99%

“…As histologic analysis has limited value in predicting the neoplastic behavior of meningiomas, human studies have evaluated proliferation markers such as Ki-67, [2][3][4][5][6][7][8] proliferating cell nuclear antigen (PCNA), 8,9 and mitosin 10 in addition to the mitotic index. 4,6,7,9,10 Ki-67 is a marker of cell proliferation that is expressed in all active phases of the cell cycle. 11 The monoclonal antibody MIB-1 labels the Ki-67 antigen and proliferation rate can be defined by the MIB-1 Labeling Index (LI), which is calculated from the percentage of positive staining cells.…”

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confidence: 99%

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Ki‐67 and Vascular Endothelial Growth Factor Expression in Intracranial Meningiomas in Dogs

Matiasek¹,

Platt²,

Adams³

et al. 2009

Veterinary Internal Medicne

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Background: Tumor proliferation in human intracranial meningiomas can be defined by the reactivity of the monoclonal antibody MIB-1 to the Ki-67 antigen. Vascular endothelial growth factor (VEGF), a pro-angiogenic factor, is a predictive marker for survival of dogs with intracranial meningiomas.Hypothesis: Ki-67 is expressed in canine intracranial meningiomas and is associated with VEGF expression. Ki-67 expression is a prognostic marker for patient outcome.Animals: Seventy client-owned dogs with WHO grade I intracranial meningiomas. Methods: Retrospective study assessing the degree of immunostaining for Ki-67 by MIB-1 and VEGF expression in intracranial meningioma tissue from dogs. MIB-1 Labeling Index (LI) was calculated with Image J NIH-software. Extent, intensity, and distribution of VEGF-expression was assessed semiquantitatively. Cross tabulations with Fisher's exact tests and nonparametric Spearman's rank correlations were performed to identify associations between VEGF expression and MIB-1 LI. Fifteen dogs underwent postsurgical radiotherapy and were included in survival analysis. The effect of MIB-1 LI on survival was examined by Kaplan-Meier and Cox proportional hazards regression procedures.Results: Ki-67 staining was positive in 91% (64/70) and VEGF expression was detected in 96% (67/70). There was no significant association between VEGF expression and MIB-1 LI. MIB-1 LI was not associated with survival.Conclusions and Clinical Importance: MIB-1 antibody can be used to document cell proliferation in intracranial meningiomas in dogs, but does not predict outcome. No association between VEGF as a marker of angiogenesis and tumor proliferation was found. Angiogenesis might be a more important predictor of meningioma activity in dogs than is Ki-67.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Ki‐67 and Vascular Endothelial Growth Factor Expression in Intracranial Meningiomas in Dogs

Matiasek¹,

Platt²,

Adams³

et al. 2009

Veterinary Internal Medicne

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“…In the present study, we investigated caspase-3 immunoreactivity in a series of intracranial, totally resected meningiomas, as a continuum of previous studies of our group, aiming to determine prognosticators of meningioma recurrence [5,[22][23][24]. Despite the importance of apoptosis in the development of central and peripheral nervous system, there are rather few reports concerning the magnitude of cell deletion in meningiomas [4][5][6][7].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2006

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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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“…Ki-67 has been claimed to be the best indicator of prognosis [3][4][5][6][7][8][9][10][11][12]. In addition to Ki-67, some novel proliferation markers such as mitosin and 2 clones of topoisomerase IIα (Ki S1 and 3F6) as well as minichromosome maintenance-2 protein have been reported to be useful [13][14][15][16]. Another marker related to proliferation is telomerase, a telomerase synthesing protein that contributes to continuous proliferation and immortality, whereas the exhaustion of telomeric repeats triggers apoptosis [17,18].…”

Section: Introductionmentioning

confidence: 99%

Does protein expression predict recurrence of benign World Health Organization grade I meningioma?

Kärjä

Sandell

Kauppinen³

et al. 2010

Human Pathology

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DNA topoisomerase IIα expression correlates with cell proliferation but not with recurrence in intracranial meningiomas

Cited by 17 publications

References 26 publications

Ki‐67 and Vascular Endothelial Growth Factor Expression in Intracranial Meningiomas in Dogs

Ki‐67 and Vascular Endothelial Growth Factor Expression in Intracranial Meningiomas in Dogs

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

Does protein expression predict recurrence of benign World Health Organization grade I meningioma?

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