Abnormalities of the p53 gene are the most common molecular change in human cancer. In the central nervous system, mutant p53 gene is frequently identified in the tumors with astrocytic differentiation. To investigate the relation between histologic subtypes and p53 protein overexpression, we examined 81 cases of astrocytic neoplasms (24 benign astrocytoma, 28 anaplastic astrocytoma and 29 glioblastoma multiforme) using the standard immunohistochemical method. All were formalin-fixed and paraffin-embedded tissue. The p53 immunoreactivity was found in 4/24 benign astrocytoma, 18/28 anaplastic astrocytoma, 22/29 glioblastoma multiforme. The degree of immunoreactivity closely correlated with histologic subtypes (p< 0.001). Overall p53 protein expression was most frequently detected in glioblastoma multiforme, but strong immunoreactivity (3+) was more frequently found in the anaplastic astrocytoma than in glioblastoma multiforme. Although the frequency of p53 protein expression is low, 4 benign astrocytoma showed distinct nuclear staining. In conclusion the malignant progression of astrocytic neoplasms may be associated with increasing expression of p53 protein.
Astrocytoma/*metabolism ; Brain Neoplasms/*metabolism ; Glioblastoma/*metabolism ; Human ; Immunohistochemistry ; Protein p53/*metabolism

Astrocytoma ; metabolism ; Glial Fibrillary Acidic Protein ; metabolism ; Humans ; In Vitro Techniques ; Nestin ; metabolism

BACKGROUNDThe RNA-binding motif protein 3 (RBM3), which is transcriptionally induced by low temperature and hypoxia, has recently been found to be upregulated in human tumors. However, its expression status in human astrocytoma is not well defned. This article focuses on the differential expression of RBM3 in human astrocytomas of different grades and normal brain tissues.

METHODSRBM3 was detected in astrocytomas and normal brain tissues by quantitative real-time PCR, immunohistochemistry, and Western blotting. Analysis of variance was performed on the data from quantitative real-time PCR. The Fisher's exact test was used to analyze the immunohistochemistry results. A P-value of less than 0.05 indicates a statistically significant difference.

RESULTSOn one hand, the mRNA expression levels of three X-chromosome-related RBM genes (RBMX, RBM3, and RBM10) were detected by quantitative real-time PCR. The results showed that there were no significant differences in RBMX and RBM10 mRNA expression levels in human astrocytomas of different grades and normal brain tissues. However, RBM3 mRNA expression levels were elevated in high-grade (World Health Organization (WHO) Grade III-IV) astrocytomas versus low-grade (WHO Grade I-II) astrocytomas (5.06 ± 0.66 vs. 1.60 ± 0.58; P < 0.05) or normal controls (5.06 ± 0.66 vs. 1.03 ± 0.22; P < 0.05) as determined by quantitative real-time PCR analysis. On the other hand, immunohistochemistry showed an increased RBM3 labeling index in astrocytomas of different grades and normal brain tissues (positive staining rate: astrocytoma Grade IV, 92.9%; astrocytoma Grade III, 81.8%; astrocytoma Grade I-II, 50%; normal brain tissues, 37.5%; high-grade astrocytoma versus normal brain tissues, P < 0.05; high-grade astrocytoma versus low-grade astrocytoma, P < 0.05). The higher protein levels of RBM3 were also validated in high-grade astrocytomas and low-grade astrocytomas compared with normal brain tissues by Western blotting.

CONCLUSIONSThese data suggest that the overexpression of RBM3 may serve as an important molecular mechanism underlying astrocytic carcinogenesis. Moreover, RBM3 may have proliferative and/or proto-oncogenic functions in human astrocytomas.

Astrocytoma ; genetics ; metabolism ; Blotting, Western ; Humans ; Immunohistochemistry ; In Vitro Techniques ; RNA-Binding Proteins ; genetics ; metabolism ; Real-Time Polymerase Chain Reaction

BACKGROUNDPrevious researches have indicated that glioma invasion may occur within a tumor-host microecology, and that fibronectin may be involved in glioma invasion as an important component of the extracellular matrix. However, how the interaction between tumor cells and vascular endothelial cells affects glioma invasion is poorly understood. The aim of this study was to investigate the effects of the interaction between tumor cells and vascular endothelial cells on glioma invasion, and the relationship of this interaction to fibronectin.

METHODSThe localization of fibronectin in different brain astrocytoma tissues was determined by immunohistochemistry. Then, vascular endothelial cells and glioma cells were co-cultured in a Transwell co-culturing system. Fibronectin expression was detected by reverse transcriptase-polymerase chain reaction, immunocytochemistry, and enzyme-linked immunosorbent assay. Additionally, the influence of the interaction between tumor cells and vascular endothelial cells on glioma cell invasion was determined by an in vitro rapid invasion test.

RESULTSIn brain astrocytoma tissues, fibronectin was present on the endothelial cells, in the extracellular matrix. Fibronectin expression was greater in higher grade tumors than in lower grade tumors. The interaction of glioma cells and vascular endothelial cells in vitro induced fibronectin release from vascular endothelial cells, which in turn stimulated glioma cell migration. This effect was inhibited by fibronectin blocking antibody.

CONCLUSIONGlioma cells may induce vascular epithelial cells to express fibronectin, and in turn fibronectin could promote glioma cell invasion.

Astrocytoma ; metabolism ; Brain Neoplasms ; metabolism ; Cell Movement ; physiology ; Cells, Cultured ; Coculture Techniques ; Enzyme-Linked Immunosorbent Assay ; Fibronectins ; metabolism ; Glioma ; metabolism ; Humans ; Immunohistochemistry ; Reverse Transcriptase Polymerase Chain Reaction

BACKGROUNDRecent studies have discovered that nuclear translocation of nerve growth factor (NGF) and its receptor fragments function differently from the traditional model. This study aimed to uncover the nuclear expression of NGF in astrocytoma and its biological significance.

METHODSNinety-four paraffin-embedded astrocytoma specimens were subjected to immunohistochemical (IHC) and hemotoxylin & eosin (HE) staining. Preoperative cerebrospinal fluid (CSF) specimens and intraoperative snap-frozen astrocytoma tissues were assayed for NGF expression by ELISA and Western blotting. The outcome of patients who contributed samples was tracked. Each ten tissue samples from patients with traumatic brain injury who had received decompression surgery and CSF samples from patients undergoing spinal anesthesia but with no history of nervous system disease were taken as control.

RESULTSNGF-positive immunoreactive products were distributed in both the cytoplasm and nucleus of astrocytoma, but were only located in the cytoplasm of traumatic brain injury (TBI) tissue. NGF nuclear-positive rate (NPR) of grades III - IV astrocytomas (70.0%) was higher than that of grades I - II astrocytoma (28.6%, P < 0.05). NGF-NP expression positively correlated with the NGF concentration in cerebrospinal fluid (CSF) (r = 0.755, P < 0.01). Kaplan-Meier survival analysis indicated that the median survival time was 25 months for NGF-NP astrocytoma grade I - II patients and 42 months in NGF nuclear negative (NGF-NN) astrocytoma grade I - II patients (P < 0.05). In astrocytoma III - IV patients, the median survival was 7 months for NGF-NP patients and 24 months for NGF-NN patients (P < 0.01). Two types of NGF with molecular weights of 13 and 36 kDa were present in astrocytoma, but only the 36 kDa NGF was found in the CSF. NGF expression elevated as the malignancy increased.

CONCLUSIONSNGF-NP expression and NGF level in CSF were significant prognostic factors in astrocytoma patients. Because of the easy access of CSF, it may be developed as an index for early diagnosis and surveillance of astrocytoma.

Astrocytoma ; metabolism ; Biomarkers ; metabolism ; Blotting, Western ; Cerebrospinal Fluid ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Nerve Growth Factor ; metabolism ; Prognosis

Astrocytoma ; genetics ; metabolism ; Brain Neoplasms ; genetics ; metabolism ; Frizzled Receptors ; genetics ; metabolism ; Glioblastoma ; genetics ; metabolism ; Glioma ; genetics ; metabolism ; Humans ; Paraffin Embedding ; RNA, Messenger ; metabolism ; Receptors, G-Protein-Coupled ; genetics ; metabolism ; Signal Transduction ; Wnt2 Protein ; genetics ; metabolism ; beta Catenin ; genetics ; metabolism

OBJECTIVE: To determine the mRNA and protein expressions of RCAS1 in human astrocytic tumors, and to explore the relation between their expression and the genesis and development of tumor. METHODS: The RCAS1 mRNA expression in human astrocytic tumors was evaluated by RT-PCR, and the RCAS1 protein expression was studied by immunohistochemical staining. RESULTS: The quantities of RCAS1 mRNA expression between diffusive astrocytoma(Grade II) and anaplastic astrocytoma(Grade III), anaplastic astrocytoma and glioblastoma(Grade IV) were significantly different(P<0.05), while the expression scores of RCAS1 protein were different only between the anaplastic astrocytoma and glioblastoma(P<0.01). RCAS1 protein expression was positively correlated with the tumor grade (r=0.573,P<0.001). The RCAS1 protein was not detected in normal brain tissues by immunohistochemical staining. CONCLUSION The RCAS1 expression is related to the histological grade of astrocytic tumor. In astrocytic tumors, the RCAS1 expression is regulated transcriptionally and posttranscriptionally.
Adolescent ; Adult ; Aged ; Antigens, Neoplasm ; genetics ; metabolism ; Astrocytoma ; genetics ; metabolism ; Brain Neoplasms ; genetics ; metabolism ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; RNA, Messenger ; genetics ; Young Adult

Astrocytoma ; metabolism ; pathology ; surgery ; Brain Neoplasms ; metabolism ; pathology ; surgery ; Child, Preschool ; Diagnosis, Differential ; Ependymoma ; metabolism ; pathology ; Female ; Follow-Up Studies ; Glial Fibrillary Acidic Protein ; metabolism ; Humans ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neurofibroma, Plexiform ; metabolism ; pathology ; S100 Proteins ; metabolism ; Vimentin ; metabolism

Astrocytoma ; pathology ; Brain Neoplasms ; metabolism ; pathology ; surgery ; Diagnosis, Differential ; Ganglioneuroma ; metabolism ; pathology ; surgery ; Glial Fibrillary Acidic Protein ; metabolism ; Humans ; Intermediate Filament Proteins ; metabolism ; Male ; Nerve Tissue Proteins ; metabolism ; Nestin ; Neurons ; pathology ; Oligodendroglioma ; pathology ; Synaptophysin ; metabolism ; Vimentin ; metabolism ; Young Adult

OBJECTIVETo detect the differential expression of Notch1 and Notch2 in human astrocytoma and medulloblastoma; and to study the role of Notch1 and Notch2 in the development of both tumors.

METHODSImmunohistochemical staining (SP method) and Western blot analysis were used to detect Notch1 and Notch2 expression in tissue arrays and freshly resected samples of normal brain tissue, astrocytoma and medulloblastoma.

RESULTSNotch1 and Notch2 were negative in normal human brain tissue. Notch1 was highly expressed (total positive rate 80.0%, 48/60) while Notch2 was not detected in grade IV astrocytomas and sporadically observed in lower grade astrocytomas (total positive rate 10.0%, 6/60). The percentage of positive tumor cells and expression level of Notch1 increased with higher histologic grade (r = 0.859, P < 0.05). On the other hand, overexpression of Notch2 was detected in medulloblastoma (9/10) in contrast with lower expression of Notch1 (2/10).

CONCLUSIONSNotch1 and Notch2 show differential expression in astrocytoma and medulloblastoma. This may be related to their different functional activities during the process of brain development.

Adolescent ; Adult ; Aged ; Astrocytoma ; metabolism ; Biomarkers, Tumor ; metabolism ; Brain ; metabolism ; Brain Neoplasms ; metabolism ; Child ; Child, Preschool ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Medulloblastoma ; metabolism ; Middle Aged ; Receptor, Notch1 ; metabolism ; physiology ; Receptor, Notch2 ; metabolism ; physiology ; Young Adult