Immunohistochemical expression of peripheral benzodiazepine receptors in human astrocytomas and its correlation with grade of malignancy, proliferation, apoptosis and survival.
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.
Vlodavsky
Eugene
E
Pathology Institute, Rambam Medical Center and Faculty of Medicine, Technion-Israel Institute of Technology, POB 9602, Haifa, Israel. e_vlodavsky@rambam.health.gov.il
Soustiel
Jean F
JF
D000704:Analysis of Variance; D017209:Apoptosis / Q000502:physiology*; D001254:Astrocytoma / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism*; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016019:Survival Analysis
D019394:Ki-67 Antigen; D018079:Receptors, GABA; C499229:TSPO protein, human