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

Dimitrios Roukas, Evangelos Tsiambas, Despoina Spyropoulou, Maria Adamopoulou, George Tsouvelas, Sofianiki Mastronikoli, Antonella-Effrosyni Monastirioti, Anastasios Kouzoupis, Andreas Lazaris, Nikolaos Kavantzas
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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.

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基于组织芯片分析的脑膜瘤亚型中 Caspase 3 的表达特征
背景/目的:在原发性中枢神经系统肿瘤中,脑膜瘤是全球成人中最常见的类型。恶性肿瘤(包括脑膜瘤)中凋亡途径的失调与化疗抗药性和不良预后有关。Caspases是诱导细胞凋亡的关键蛋白。本研究旨在将 Caspase 3 蛋白表达水平与脑膜瘤临床病理特征相关联:本研究分析了50个(n=50)脑膜瘤病变,包括广泛的组织病理学亚型(脑膜肉瘤型、脓瘤型、过渡型、纤维型、血管瘤型、微囊型、非典型型和无弹性型)。采用抗天冬酶 3 抗体对所选石蜡块的组织微阵列核心进行免疫组化。此外,还对相应的免疫染色切片进行了图像分析:结果:在 17/50 例(34%)病例中检测到 Caspase 3 蛋白过度表达,而其余 33 例(66%)病例的 Caspase 3 蛋白表达水平为中低水平。据统计,Caspase 3 的表达与所分析肿瘤的分级和有丝分裂指数有显著相关性(分别为 p=0.002 和 p=0.001)。Caspase 3的表达状态还与所选脑膜瘤的组织型相关(p=0.016):Caspase3在相当一部分受检脑膜瘤中的低表达水平与分化等级、有丝分裂活性相关,部分与特定组织型相关。能提高 Caspase 3 表达--诱导其凋亡活性--的药物是肿瘤学中一个非常有希望开发出新型治疗方案的领域。
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