Caspase 3 Expression Profiles in Meningioma Subtypes Based on Tissue Microarray Analysis

Overview

Journal Cancer Diagn Progn

Specialty Oncology

Date 2024 Sep 6

PMID 39238614

Authors

Dimitrios Roukas

Evangelos Tsiambas

Despoina Spyropoulou

Maria Adamopoulou

George Tsouvelas

Sofianiki Mastronikoli

Antonella-Effrosyni Monastirioti

Anastasios Kouzoupis

Andreas Lazaris

Nikolaos Kavantzas

Affiliations

Soon will be listed here.

Abstract

Background/aim: Concerning primary central nervous system neoplasms, meningiomas demonstrate the most common type in adults worldwide. Deregulation of apoptotic pathways in malignancies, including meningiomas, is correlated with chemoresistance and poor prognosis. Caspases represent crucial proteins that induce cell apoptosis. This study aimed to correlate caspase 3 protein expression levels to meningioma clinic-pathological features.

Materials And Methods: A set of fifty (n=50) meningioma lesions was included in the current analysis including a broad spectrum of histopathological subtypes (meningotheliomatous, psammomatus, transitional, fibrous, angiomatous, microcystic, atypical and anaplastic). Immunohistochemistry was implemented on tissue microarray cores of selected paraffin blocks by applying an anti-caspase 3 antibody. Additionally, an image analysis protocol was also performed in the corresponding immunostained slides.

Results: Caspase 3 protein over-expression was detected in 17/50 (34%) cases, whereas the remaining 33 cases (66%) were characterized by medium to low levels of the molecule. Caspase 3 expression was statistically significantly associated with the grade of the analyzed tumors and the mitotic index (p=0.002, p=0.001, respectively). Caspase 3 expression status was also correlated with the histotype of the selected meningiomas (p=0.016).

Conclusion: Caspase 3 demonstrated low expression levels in a significant subset of the examined meningiomas correlated with differentiation grade, mitotic activity, and partially with specific histotypes. Agents that could enhance caspase 3 expression - inducing its apoptotic activity - represent a very promising area in oncology for developing novel treatment regimens.

References

Kawamura Y, Hua L, Gurtner A, Wong E, Kiyokawa J, Shah N . Histone deacetylase inhibitors enhance oncolytic herpes simplex virus therapy for malignant meningioma. Biomed Pharmacother. 2022; 155:113843. PMC: 9590235. DOI: 10.1016/j.biopha.2022.113843. View

Ray S, Patel S, Welsh C, Wilford G, Hogan E, Banik N . Molecular evidence of apoptotic death in malignant brain tumors including glioblastoma multiforme: upregulation of calpain and caspase-3. J Neurosci Res. 2002; 69(2):197-206. DOI: 10.1002/jnr.10265. View

Sasaki T, Lopes M, Hankins G, Helm G . Expression of survivin, an inhibitor of apoptosis protein, in tumors of the nervous system. Acta Neuropathol. 2002; 104(1):105-9. DOI: 10.1007/s00401-002-0532-x. View

Arumugam A, Razis A . Apoptosis as a Mechanism of the Cancer Chemopreventive Activity of Glucosinolates: a Review. Asian Pac J Cancer Prev. 2018; 19(6):1439-1448. PMC: 6103590. DOI: 10.22034/APJCP.2018.19.6.1439. View

Pislar A, Jewett A, Kos J . Cysteine cathepsins: Their biological and molecular significance in cancer stem cells. Semin Cancer Biol. 2018; 53:168-177. DOI: 10.1016/j.semcancer.2018.07.010. View

Maes L, Kalala J, Cornelissen R, de Ridder L . Telomerase activity and hTERT protein expression in meningiomas: an analysis in vivo versus in vitro. Anticancer Res. 2006; 26(3B):2295-300. View

Pfeffer C, Singh A . Apoptosis: A Target for Anticancer Therapy. Int J Mol Sci. 2018; 19(2). PMC: 5855670. DOI: 10.3390/ijms19020448. View

Banoth B, Cassel S . Mitochondria in innate immune signaling. Transl Res. 2018; 202:52-68. PMC: 6218307. DOI: 10.1016/j.trsl.2018.07.014. View

Tang M, Wei H, Han L, Deng J, Wang Y, Yang M . Whole-genome sequencing identifies new genetic alterations in meningiomas. Oncotarget. 2017; 8(10):17070-17080. PMC: 5370023. DOI: 10.18632/oncotarget.15043. View

10.

Tong Y, Mentlein R, Buhl R, Hugo H, Krause J, Mehdorn H . Overexpression of midkine contributes to anti-apoptotic effects in human meningiomas. J Neurochem. 2006; 100(4):1097-107. DOI: 10.1111/j.1471-4159.2006.04276.x. View

11.

Ozdogan S, Kafadar A, Yilmaz S, Timirci-Kahraman O, Gormus U, Isbir T . Role of Caspase-9 Gene Ex5+32 G>A (rs1052576) Variant in Susceptibility to Primary Brain Tumors. Anticancer Res. 2017; 37(9):4997-5000. DOI: 10.21873/anticanres.11912. View

12.

Nagahama A, Yashiro M, Kawashima T, Nakajo K, Morisako H, Uda T . Combination of p53 and Ki67 as a Promising Predictor of Postoperative Recurrence of Meningioma. Anticancer Res. 2021; 41(1):203-210. DOI: 10.21873/anticanres.14766. View

13.

Yamamoto M, Suzuki S, Togashi K, Sugai A, Okada M, Kitanaka C . Gemcitabine Cooperates with Everolimus to Inhibit the Growth of and Sensitize Malignant Meningioma Cells to Apoptosis Induced by Navitoclax, an Inhibitor of Anti-Apoptotic BCL-2 Family Proteins. Cancers (Basel). 2022; 14(7). PMC: 8997110. DOI: 10.3390/cancers14071706. View

14.

Meredith D . Advances in Diagnostic Immunohistochemistry for Primary Tumors of the Central Nervous System. Adv Anat Pathol. 2019; 27(3):206-219. DOI: 10.1097/PAP.0000000000000225. View

15.

Takeda H, Okada M, Kuramoto K, Suzuki S, Sakaki H, Sanomachi T . Antitumor activity of gemcitabine against high-grade meningioma and . Oncotarget. 2017; 8(53):90996-91008. PMC: 5710900. DOI: 10.18632/oncotarget.18827. View

16.

Bhattacharyya S, Oblinger J, Beauchamp R, Yin Z, Erdin S, Koundinya P . Proteasomal pathway inhibition as a potential therapy for NF2-associated meningioma and schwannoma. Neuro Oncol. 2023; 25(9):1617-1630. PMC: 10479743. DOI: 10.1093/neuonc/noad037. View

17.

Tirapelli D, Menezes S, Franco I, Lustosa I, Rodrigues A, Novais P . High expression of anti-apoptotic genes in grade I and II meningiomas. Arq Neuropsiquiatr. 2017; 75(4):209-215. DOI: 10.1590/0004-282X20170027. View

18.

Chiou H, Lai W, Huang L, Huang S, Chueh S, Ma H . Valproic acid promotes radiosensitization in meningioma stem-like cells. Oncotarget. 2015; 6(12):9959-69. PMC: 4496410. DOI: 10.18632/oncotarget.3692. View

19.

Chung C . Restoring the switch for cancer cell death: Targeting the apoptosis signaling pathway. Am J Health Syst Pharm. 2018; 75(13):945-952. DOI: 10.2146/ajhp170607. View

20.

Roukas D, Kouzoupis A, Spyropoulou D, Papanastasiou G, Tsiambas E, Tsouvelas G . P53 Suppressor Gene Tissue Microarray-based Protein Expression Analysis in Meningiomas. In Vivo. 2022; 36(5):2205-2210. PMC: 9463907. DOI: 10.21873/invivo.12946. View