Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Due to the low incidence of intramedullary spinal cord tumors there have been few reports considering its proliferative kinetics. In this study, expression of two cell cycle related antigens (PCNA and MIB-1) were immunohistochemically examined by the percentage of positively stained cells were recorded as PCNA and MIB-1 indices. In addition, over-expression of p53 protein was also investigated in 19 cases of intrameduallary spinal cord tumors. In astrocytic tumors and ependymomas, statistically significant correlations were observed between PCNA and MIB-1 indices (R = 0.98). In hemangioblastoma cases, a similar correlation was not observed between PCNA and MIB-1 indices. The MIB-1 indices of hemangioblastoma cases were less than 1.56 while PCNA indices were more than 14.63 despite long-term survival occurred in all cases. The PCNA index in hemangioblastoma was significantly greater (p < 0.01) than all other types of tumors except for glioblastomas. Thus, interpretation of PCNA index must be made with caution in regard to the subgroup of the tumor histology. Over-expression of the p53 protein was observed only in glioblastoma cases. The MIB-1 index appears to be a useful method for predicting the outcome of all cases with intramedullary tumors of the spinal cord.
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PMID:Significance of MIB-1, PCNA indices, and p53 protein over-expression in intramedullary tumors of the spinal cord. 891 30

The presence of gemistocytes in low-grade astrocytomas is regarded as a sign of poor prognosis because the majority of gemistocytic astrocytomas rapidly progress to anaplastic astrocytoma or glioblastoma. To elucidate the role of gemistocytes in astrocytoma progression, we assessed the fraction of neoplastic gemistocytes, bcl-2 expression, p53 mutations, p53 immunoreactivity (PAb 1801), and proliferative activity (MIB-1) in 40 low-grade astrocytomas (World Health Organization (WHO) Grade II) with histologically proven progression to anaplastic astrocytoma (WHC Grade III) or glioblastoma (WHO Grade IV). Astrocytoma progression took significantly less time in patients with a low-grade astrocytoma containing more than 5% gemistocytes (35 months) than in those with lesions containing less than 5% gemistocytes (64 months; p = 0.038). All 11 astrocytomas with more than 5% gemistocytes contained a p53 mutation, whereas the incidence of p53 mutations in astrocytomas with less than 5% gemistocytes was 61% (p = 0.017). In low-grade astrocytomas the p53 labeling index (LI) of gemistocytes (7.4%) was significantly higher than in all tumor cells (3.2%, p = 0.0014). Gemistocytes showed a significantly higher bcl-2 expression than all tumor cells, with a mean bcl-2 1 of 15.6% versus 2.7% in low-grade astrocytomas (p = 0.0004), 20.9% versus 3.0% in anaplastic astrocytoma (p = 0.002), and 30.2% versus 5.2% in glioblastomas (p = 0.0002). In contrast, gemistocytes showed a significantly lower proliferating activity than the mean of all tumor cells, with a mean MIB-1 LI of 0.5% versus 2.6% in low-grade astrocytomas, 1.5% versus 11.6% in anaplastic astrocytoma, and 1.7% versus 16.6% in glioblastomas (p < 0.0001). These data show that low-grade astrocytomas with a significant fraction of gemistocytes progress more rapidly and typically carry a p53 mutation. The vast majority of gemistocytes are, however, in a nonproliferative state (G0 phase of the cell cycle), which suggests terminal differentiation. Their accumulation within astrocytomas may be due to bcl-2-mediated escape from apoptosis.
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PMID:Role of gemistocytes in astrocytoma progression. 904 64

Cell proliferation and invasion were studied in sixty biopsies of malignant gliomas selected to reproduce the spreading modalities identified in ninety autopsy cases of glioblastoma. Cell proliferation was studied by the immunohistochemical demonstration of PCNA and MIB-1 and by the calculation of their labeling indexes (LI). The main finding was that cell proliferation and cell invasion are not necessarily associated. The interface between the solid tumor and the adjacent brain was represented either by a gradient of tumor cell density or by a clearcut demarcation of the tumor. In the first case the LI either did not change in the infiltration area in comparison with solid tumor or it was much lower, whereas in the second case there was a ring with a high density of labeled nuclei at the tumor periphery. Perineuronal satellites were usually positive for proliferation markers. Cells accumulated in the outer cortical layers, from a deeply located tumor, were almost negative, whereas those originating from subarachnoidal or subpial invasion showed a high LI. High LIs were also found in subarachnoidal and subpial growths, and in a cell population descending into the brain parenchyma around meningeal penetrating vessels. The relationship between cell proliferation and invasion from in vivo studies is not a direct and a simple one.
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PMID:Cell proliferation and invasion in malignant gliomas. 906 31

Proliferative activity in 78 glioma specimens was assessed immunohistochemically by determining proliferating index of tumor cells (PTC-PI) and endothelial cells (PEC-PI) using the MIB-1 monoclonal antibody. The PTC-PI of anaplastic astrocytoma (9.0 +/- 5.8: mean + standard deviation) was significantly higher than that of astrocytoma (1.2 +/- 0.4, < 0.01), and lower than that of glioblastoma multiforme (12.0 +/- 5.6, < 0.05). We then compared PTC-PI values with the prognosis of patients with malignant glioma (both glioblastoma and anaplastic astrocytoma). Kaplan-Meier survival rate analysis demonstrated higher survival rates in patients with less than 8.0% of PTC-PI at 5 and 10 years (p < 0.05). These results suggested PTC-PI provides useful information which may allow better assessment of the biological behaviour and clinical prognosis of glioma, in addition to histological grading. While the average PEC-PI value (3.3) was lower than that of PTC-PI (7.0), there was a significantly close relationship between them (p < 0.01), fostering the developments novel therapies directed towards suppression of microvascular regeneration.
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PMID:Proliferative potentials of glioma cells and vascular components determined with monoclonal antibody MIB-1. 926 40

To prognosticate the implications of various allelic losses on chromosome 17 in the morphology and biology of astrocytic tumors, we have examined loss of heterozygosity (LOH) at 14 microsatellite loci on chromosome 17 in a series of 19 astrocytic tumors (3 astrocytomas, 5 anaplastic astrocytomas, and 11 glioblastomas). The DNA samples extracted from tumor and matched normal brain tissue were amplified by polymerase chain reaction (PCR) followed by polyacrylamide gel electrophoresis and photography under UV transillumination. The molecular genetic data were compared with immunohistochemistry performed with antibodies to glial fibrillary acidic protein (GFAP), MIB-1 and p53 protein. LOH was observed in 11/19 (58%) instances with frequent involvement of TP53, NF1, and D17S795 loci, LOH at D17S578 and D17S520 occurred in recurrent tumors exclusively. Allelic status of D17S795 in all 12 informative instances were concordant with GFAP immunoreactivity (p < 0.01, Fisher's test). p53 immunopositivity (> 25% of tumor cell nuclei) was seen in 11 (58%) tumors, of which 6 were informative of TP53 locus with 2 (33%) demonstrating LOH. The MIB-1 staining indexes in astrocytomas, anaplastic astrocytomas, and glioblastomas were 1.9 +/- 0.9, 8.4 +/- 4.0, and 17.1 +/- 7.1% (mean +/- SD), respectively, and their differences were statistically significant (p < 0.05, Student's t test). A trend of inverse relationship between patient survival and the number of tumor cell nuclei with immunohistochemically detectable p53 protein was seen in glioblastoma cases: 20.5 +/- 12.7 versus 13.7 +/- 6.3 months (mean +/- SD) in instances with > or > or = 25% positive cells, respectively. We conclude, the intriguing correlation between allelic status of D17S795 microsatellite locus and GFAP immunoreactivity suggests the possible involvement of q21.2 segment of chromosome 17 in the morphology and biology of astrocytic tumors.
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PMID:Chromosome 17 allelic loss in astrocytic tumors and its clinico-pathologic implications. 926 49

Proliferative activity in 78 glioma specimens was assessed immunohistochemically by determining proliferating index of tumor cells (PTC-PI) and endothelial cells (PEC-PI) using the MIB-1 monoclonal antibody. The PTC-PI of anaplastic astrocytoma (9.0 +/- 5.8: mean +/- standard deviation) was significantly higher than that of astrocytoma (1.2 +/- 0.4, < 0.01), and lower than that of glioblastoma multiforme (12.0 +/- 5.6, < 0.05). We then compared PTC-PI values, patients' age and extent of tumor resection with the prognosis of patients with malignant glioma (both glioblastoma and anaplastic astrocytoma). Kaplan-Meier survival rate analysis demonstrated higher survival rates in patients with less than 8.0% of PTC-PI at 5 and 10 years (p < 0.05). The mean age of patients who survived more than a year was lower than that of patients who died within a year (53.0 y.o., vs. 59.7 y.o., p < 0.01). Total or subtotal resection of the tumor was more often performed in the former than latter patients (51% vs. 21%, p < 0.01). These results suggested PTC-PI provides useful information which may allow better assessment of the biological behavior and clinical prognosis of glioma, in addition to histological grading, patients' age and extent of tumor resection. While the average PEC-PI value (3.3) was lower than that of PTC-PI (7.0), there was a significantly close relationship between PTC- and PEC values (p < 0.01), providing an impetus to develop novel therapies directed toward suppression of microvascular regeneration.
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PMID:Proliferative potentials of glioma cells and vascular components determined with monoclonal antibody MIB-1. 950 11

Immunohistochemistry (IHC) has provided major insights about the classification of brain tumors by identifying cellular markers of phenotype and about tumor growth potential with nuclear markers of proliferation. In situ hybridization (ISH) research shows promise for diagnostic applications in tumor classification. The avidin-biotin conjugate IHC procedure is highlighted for diagnostic use on routinely processed clinical specimens. The immunophenotypes of brain tumors are tabulated in reference to their common IHC markers. Tumors that have been correctly classified by their IHC phenotypes include the giant-cell glioblastoma, primary brain lymphoma, and central neurocytoma. Phenotypes that may be more definitively detected by ISH, such as pituitary hormone, immunoglobulin light chain, and collagen messages are described. IHC of nuclear proliferation markers correlates with grade of malignancy, predicts tumor growth potential, and is prognostic for patient survival. The incorporation of bromodeoxyuridine, the expression of proliferating cell nuclear antigen, and the expression of Ki-67 antigen detected by MIB-1 antibody are compared in regard to their cell cycle activity and labeling index determinations. Fluorescence in situ hybridization (FISH) of brain tumor interphase nuclei and chromosomes is described. Abnormal FISH signals of specific chromosomes are associated with different types of brain tumors, with different grades of malignancy, and with mesenchymal drift of glioma cells in culture.
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PMID:Insights about brain tumors gained through immunohistochemistry and in situ hybridization of nuclear and phenotypic markers. 960 6

Three cases of primary gliosarcoma (GS) were studied by immunohistochemical, ultrastructural and fluorescence in situ hybridization (FISH) methods. All tumors occurred in the supratentorial regions of the body. No patient had a prior history of irradiation to the brain. All patients died of tumor within 1 year, and autopsies were performed in two cases. Microscopically, each of the three tumors showed a mixture of glioblastoma (GBM) and a sarcomatous component (SC), which resembled fibrosarcoma with various histological features. Numerous collagen and reticulin fibers were seen in the SC of all tumors. Glial fibrillary acidic protein (GFAP) was immunoreactive only in the gliomatous component (GC). Factor VIII-related antigen was negative except for endothelial cells. One tumor exhibited alpha-smooth muscle actin positivity in the SC. Expression of MIB-1 and p53 protein was demonstrated in both components for all tumors. Labeling indices (LI) for MIB-1 ranged from 7.7 to 36.1%, and LI for p53 protein ranged from 2.9 to 57.0%. Ultrastructurally, astrocytic cells were characterized by a polygonal configuration with many cytoplasmic projections and occasional filaments. Spindle-shaped fibroblasts in the SC contained well-developed rough endoplasmic reticulum. Fluorescence in situ hybridization (FISH) performed on fresh materials or paraffin-embedded tissue demonstrated single signals for chromosome 10 in 40.6-58.3% of cells and for chromosome 17 in 37.9-48.6% of cells. Two tumors were regarded as containing losses of both chromosomes 10 and 17, while the third showed a substantial loss only of chromosome 10. As similar aberrations have been reported in GBM, these chromosomal abnormalities suggest a common pathogenesis in GS and GBM.
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PMID:Gliosarcoma: an immunohistochemical, ultrastructural and fluorescence in situ hybridization study. 973 6

Low-grade diffuse astrocytomas have an intrinsic tendency for malignant progression but the factors determining the kinetics of this process are still poorly understood. We report here the case of a male patient who developed a fibrillary astrocytoma at the age of 33 years and who underwent six surgical interventions over a period of 17 years without radiotherapy or chemotherapy. The first three biopsies spanned a period of 11 years and led to the diagnosis of low-grade, diffuse astrocytoma (WHO grade II), with a growth fraction (MIB-1 labeling index) of 2.3-3.7%. The fourth to sixth biopsies showed histological features of anaplastic astrocytoma (WHO grade III), with growth fractions between 5.0 and 10.5%. The fraction of gemistocytic neoplastic astrocytes also increased, from 0.3% in the first biopsy to 17.5% in the last biopsy and preceded the increase in proliferative activity and transition to anaplastic astrocytoma. The fraction of tumor cells immunoreactive to BCL-2 increased from 0.3% to 8.2%. A p53 mutation in codon 273 (CGT-->TGT, Arg-->Cys) was identified in the first biopsy and persisted throughout the course of the disease. However, the fraction of cells with p53 protein accumulation increased significantly during progression, from 3.2% in the first biopsy to 13.7% in the last. The absence of additional genetic alterations (PTEN mutations, loss of chromosome 10 and 19q) may be responsible for the slow progression and lack of glioblastoma features even after a 17-year disease duration.
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PMID:A case history of glioma progression. 1033 92

Loss of chromosome 10 was assessed in 17 specimens of glioblastoma (GBM) by fluorescence in situ hybridization (FISH) technique using the centromere probe for chromosome 10. Cytospinned smear specimens were prepared from paraffin-embedded specimens. The percentage of nuclei containing a single fluorescent signal ranged from 19.2 to 88. 0% (mean, 49.3%). Thirteen tumors (76.5%) were designated as monosomy 10 because the proportion of single-signal nuclei exceeded the cut-off value (31.5%: mean of five control materials +3 standard deviations). The results confirmed the importance of the loss of chromosome 10 for the development of GBM, although no significant correlation was demonstrated between the loss of chromosome 10 and survival. In addition, proliferation potential and angiogenesis of GBM were immunohistochemically analyzed using antibodies against Ki-67 antigen (MIB-1), factor VIII-related antigen (FVIII R/Ag) and vascular endothelial growth factor (VEGF), respectively. The labeling indices of MIB-1 (1.5-57.8%) and the number of blood vessels immunoreactive for FVIII R/Ag (18-279/10 high-power fields) were not significantly related to the loss of chromosome 10. Vascular endothelial growth factor immunoreactivity in areas microvessels were counted was seen in 12 cases. However, neither the loss of chromosome 10 nor number of vessels was not correlated with VEGF expression. Other genetic abnormalities as well as loss of chromosome 10 may be involved in the cell proliferation and angiogenesis of GBM.
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PMID:Loss of chromosome 10 in glioblastoma: relation to proliferation and angiogenesis. 1050 34


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