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H3K27me3和Ki-67标记指数在评估脑膜瘤生物学行为中的作用

Role of H3K27me3 and Ki-67 Labeling Index in Assessing the Biological Behavior of Meningiomas.

作者信息

Deshpande Shalaka, Nayal Bhavna, Nair Rajesh, Nayak Deepak, J Padmapriya, V Geetha

机构信息

Department of Pathology, HBTMC and Dr. R.N. Cooper Municipal General Hospital, Mumbai, Maharashtra, India.

Department of Pathology, Kasturba Medical College, Manipal, MAHE, Karnataka, India.

出版信息

World Neurosurg. 2025 Feb;194:123514. doi: 10.1016/j.wneu.2024.11.097. Epub 2024 Dec 24.

Abstract

BACKGROUND

Meningiomas are neoplasms primarily originating from arachnoid cells and are classified into 3 grades (1, 2, and 3) based on histological features according to the World Health Organization classification. However, this classification system is imperfect especially for grade 1 and 2 meningiomas as many grade 1 tumors recur. Meningiomas are hence a histologically diverse class of tumors exhibiting more unpredictable behavior. Therefore, more improved classification is required, possibly using novel and more dependable biomarkers. In this study, we aim to investigate the role of the H3K27me3 and Ki-67 labeling index (LI) in assessing the biological behavior of meningiomas. The study was conceived, with the primary objective of examining the expression of H3K27me3 and Ki-67 LI in grade 1/2 meningiomas with atypical features to ascertain if this potentially impacts patient prognosis.

METHODS

Upon obtaining clearance from the Institutional Ethical Committee, the authors studied 81 cases of meningiomas including 11 recurrent cases. The study used immunohistochemistry to evaluate the Ki-67 index and H3K27me3 immunohistochemistry. The Ki-67 LI was determined by counting the positively stained MIB-1 cells and categorizing them into <5%, 5%-10%, and >10%. The H3K27me3 staining was evaluated by finding the product of the tumor cells showing positive staining and the intensity of staining. Based on the product of the two, the cases were subdivided into negative (0), low (1-4), and high expression (5-9) of H3K27me3.

RESULTS

The results showed that the presence of atypical morphological features including necrosis and prominent nucleoli in grade 1 meningioma and low expression of H3K27me3 was significantly associated with higher grade, recurrence, and shorter progression-free survival (Kaplan-Meier curves showed higher negative slope). The study also found that a higher Ki-67 LI was associated with recurrence and poor prognosis. This suggests that the H3K27me3 and Ki-67 LI can be useful prognostic markers in meningiomas, particularly in challenging grade 1 and 2 cases and recurrent meningiomas.

CONCLUSIONS

The study highlights the importance of the H3K27me3 and Ki-67 LI in assessing the biological behavior of meningiomas. The findings provide valuable insights into the prognosis and treatment of meningiomas, emphasizing the need for further research to validate these markers and develop targeted therapeutic strategies.

摘要

背景

脑膜瘤是主要起源于蛛网膜细胞的肿瘤,根据世界卫生组织的分类,基于组织学特征可分为3级(1级、2级和3级)。然而,这种分类系统并不完善,尤其是对于1级和2级脑膜瘤,因为许多1级肿瘤会复发。因此,脑膜瘤是一类组织学上多样的肿瘤,其行为更难以预测。所以,需要更完善的分类,可能要使用新的、更可靠的生物标志物。在本研究中,我们旨在探讨H3K27me3和Ki-67标记指数(LI)在评估脑膜瘤生物学行为中的作用。本研究的构思主要目的是检测具有非典型特征的1/2级脑膜瘤中H3K27me3和Ki-67 LI的表达,以确定这是否可能影响患者预后。

方法

在获得机构伦理委员会批准后,作者研究了81例脑膜瘤病例,包括11例复发病例。该研究使用免疫组织化学评估Ki-67指数和H3K27me3免疫组织化学。通过计数阳性染色的MIB-1细胞并将其分为<5%、5%-10%和>10%来确定Ki-67 LI。通过计算显示阳性染色的肿瘤细胞数量和染色强度来评估H3K27me3染色。根据两者的乘积,将病例分为H3K27me3阴性(0)、低表达(1-4)和高表达(5-9)。

结果

结果显示,1级脑膜瘤中存在包括坏死和明显核仁在内的非典型形态学特征以及H3K27me3低表达与更高分级、复发和更短的无进展生存期显著相关(Kaplan-Meier曲线显示负斜率更高)。该研究还发现,较高的Ki-67 LI与复发和不良预后相关。这表明H3K27me3和Ki-67 LI可作为脑膜瘤有用的预后标志物,特别是在具有挑战性的1级和2级病例以及复发性脑膜瘤中。

结论

该研究强调了H3K27me3和Ki-67 LI在评估脑膜瘤生物学行为中的重要性。这些发现为脑膜瘤的预后和治疗提供了有价值的见解,强调需要进一步研究以验证这些标志物并制定靶向治疗策略。

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