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外周苯二氮䓬受体在人脑星形细胞瘤中的免疫组化表达及其与恶性程度、增殖、凋亡和生存的相关性

Immunohistochemical expression of peripheral benzodiazepine receptors in human astrocytomas and its correlation with grade of malignancy, proliferation, apoptosis and survival.

作者信息

Vlodavsky Eugene, Soustiel Jean F

机构信息

Pathology Institute, Rambam Medical Center and Faculty of Medicine, Technion-Israel Institute of Technology, POB 9602, Haifa, Israel.

出版信息

J Neurooncol. 2007 Jan;81(1):1-7. doi: 10.1007/s11060-006-9199-9. Epub 2006 Jul 26.

Abstract

Peripheral benzodiazepine receptors (PBR) are widely distributed in peripheral tissues, astrocytes, and microglia of the brain. They are involved in apoptosis, proliferation, and many other processes, such as steroidogenesis in adrenal glands, male and female gonads, biological adaptation to stress, etc. It has been established that the expression of PBR in astrocytomas is higher than in the normal brain. The goal of this study was to explore the correlation of the immunohistochemical expression of PBR in astrocytomas with the grade of malignancy and rates of apoptosis, proliferation and survival. In 130 cases of astrocytomas (25 grade I, 25 grade II, 20 grade III, 60 grade IV), paraffin sections were stained immunohistochemically for PBR and MIB-1(Ki-67). TUNEL assay was used for evaluation of apoptosis. It was found that the intensity and extent of staining for PBR had a strong direct correlation with the grade of malignancy of the tumor, along with proliferative and apoptotic indices. The highest expression of PBR was in glioblastomas grade IV, especially around areas of necrosis. There was a strong negative correlation between PBR expression and survival. The results of this study may be applied in the pathological diagnosis of astrocytomas as an additional clue in establishing tumor grade; they may be used in the imaging of astrocytomas, both for diagnosis and follow-up, by the application of positron emission tomography scanning with PBR specific ligands. Targeting of PBR in high-grade gliomas may be a promising approach, achieving more specific anti-tumor effect.

摘要

外周苯二氮䓬受体(PBR)广泛分布于外周组织、脑内星形胶质细胞和小胶质细胞中。它们参与细胞凋亡、增殖以及许多其他过程,如肾上腺、雄性和雌性性腺中的类固醇生成、对压力的生物学适应等。已证实星形细胞瘤中PBR的表达高于正常脑。本研究的目的是探讨星形细胞瘤中PBR免疫组化表达与恶性程度、凋亡率、增殖率及生存率之间的相关性。对130例星形细胞瘤(I级25例、II级25例、III级20例、IV级60例)石蜡切片进行PBR和MIB-1(Ki-67)免疫组化染色。采用TUNEL法评估细胞凋亡。结果发现,PBR染色的强度和范围与肿瘤的恶性程度、增殖和凋亡指数呈强烈正相关。PBR的最高表达见于IV级胶质母细胞瘤,尤其是在坏死区域周围。PBR表达与生存率呈强烈负相关。本研究结果可应用于星形细胞瘤的病理诊断,作为确定肿瘤分级的额外线索;通过应用PBR特异性配体进行正电子发射断层扫描,可将其用于星形细胞瘤的成像诊断和随访。针对高级别胶质瘤中的PBR可能是一种有前景的方法,可实现更具特异性的抗肿瘤效果。

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