ABSTRACT
Background: Patients with Glioblastoma multiforme (GBM) have a five years survival of less than 5%, but the response to chemotherapy with alkylating agents can vary depending on the methylation status of O6-methylguanine-DNA-methyltransferase (MGMT). Genetic testing has limitations for routine use, while immunohistochemistry (IHC) offers a fast and affordable technique but with heterogeneous results in the literature. Aim: To evaluate MGMT expression by IHC in tumor tissue of Chilean patients with GBM. Material and Methods: Tumor samples of 29 patients with a pathological diagnosis of GBM were studied. We performed IHC staining and manual analysis of positive and negative cells for MGMT expression. A cut-off of at least 10% of cells expressing MGMT was used. Demographic and clinical features of patients were obtained from clinical records. Results: The median number of cells counted per case was 692 (interquartile range [IQR] 492-928). Fifteen cases (52%) were positive for MGMT expression. Median overall survival was 5.3 months (IQR 3.4-12-8). The effect of MGMT expression on the therapeutic response was not studied since only 3 patients received chemotherapy. Conclusions: Our results are similar to international reports, but we were not able to determine the association between MGMT expression and therapeutic response.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Brain Neoplasms/enzymology , Biomarkers, Tumor/metabolism , Glioblastoma/enzymology , O(6)-Methylguanine-DNA Methyltransferase/metabolism , Prognosis , Brain Neoplasms/genetics , Immunohistochemistry , Biomarkers, Tumor , Gene Expression Regulation, Neoplastic , Chile , Survival Rate , Retrospective Studies , Glioblastoma/genetics , O(6)-Methylguanine-DNA Methyltransferase/geneticsABSTRACT
Telomere length maintenance is regarded as a fundamental step in tumorigenesis, as most human brain tumors, including meningiomas, stabilize the ends of their chromosomes using telomerase. This investigation represents an introduction to telomerase expression in canine and feline meningiomas. Twenty-five archived cases (14 dogs and 11 cats) were immunohistochemically tested for human-telomerase reverse transcriptase (h-TERT), scored, and quantified; furthermore, mitoses were counted on sections stained with a modified toluidine blue. The h-TERT antibody immunolabelled the nucleus and nucleolus of meningeal neoplastic cells, with an intensity ranging from mild to strong and a speckled distribution; a significantly higher expression in cats was noted, while no significant association between h-TERT immunolabelling and sex or histotype was evident in dogs or cats. The telomerase enzyme represents a fundamental parameter of potential malignant transformation, which may occur independently of the signal to proliferate, thereby supplying the cells with unlimited growth capabilities. Telomerase expression could be a prognostic indicator independent of the kinetic parameters, although this should be evaluated using a larger dataset with available clinical information.
Subject(s)
Animals , Cats , Dogs , Female , Male , Brain Neoplasms/enzymology , Cat Diseases/enzymology , Dog Diseases/enzymology , Immunohistochemistry/veterinary , Meningioma/enzymology , Mitosis/physiology , Regression Analysis , Telomerase/biosynthesisABSTRACT
Telomerase adds telomeric repeats to the ends of telomeres to compensate for their progressive loss. A favorable prognosis is associated with low or no telomerase in some tumors. The authors investigated whether telomerase activity is associated with survival of patients with brain tumors. Sixty-two consecutive patients with brain tumors underwent surgery, and their surgical specimens were investigated. The patients were pathologically categorized as group I (aggressive group) and group II (non-aggressive group). Telomerase activity was examined by the telomeric repeat amplification protocol (TRAP) assay. The median time was calculated in association with overall survival and progression-free survival in each group. The significant difference was noted in telomerase activity between high-grade gliomas and lowgrade gliomas (p=0.022). Telomerase activity was significantly associated with the median overall survival and progression-free survival in all tumors of the aggressive group. On the other hand, the median overall survival in the non-aggressive group was not dependent on telomerase activity, while the median progression-free survival was. Our data suggests that telomerase is an important prognostic indicator of survival in patients with brain tumors.
Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Brain Neoplasms/enzymology , Enzyme-Linked Immunosorbent Assay/methods , Polymerase Chain Reaction/methods , Prognosis , Survival Analysis , Telomerase/geneticsABSTRACT
To evaluate possible roles of matrix metalloproteinase (MMP)-1, -2, tissue inhibitor of metalloproteinase (TIMP)-1, -2 and membrane-type-1 matrix metalloproteinase (MT1-MMP) in invasion of human gliomas, expressions of these proteins were investigated in ten cases of human glioma and two meningioma tissues and eight human glioma cell lines. In gelatin zymography, MMP-2 activities of glioblastomas were higher than astrocytomas. The activated form of MMP-2 was seen in five of six cases of glioblastomas, but not in astrocytomas. MMP-9 activity was detected in all cases of malignant astrocytomas but the reactivity of MMP-9 was weaker than that of MMP-2. MT1-MMP mRNA expression in glioblastomas was higher than that in astrocytomas. Five cases of glioblastomas with activated form of MMP-2 had MT1-MMP expressions. In vitro, human glioma cell lines with high expression of MT1-MMP also showed high MMP-2 activity. TIMP-1 transcripts were constitutively present in almost all glioma tissues and cell lines, whereas TIMP-2 mRNA were weak especially in malignant gliomas. Imbalance of TIMP-2/MMP-2 was observed using immunoprecipitation analysis in a glioma cell line. High expression of MMP-2 and MT1-MMP is possibly involved in invasiveness of malignant glioma.
Subject(s)
Humans , Animals , Blotting, Northern/methods , Brain/pathology , Brain Neoplasms/pathology , Brain Neoplasms/enzymology , Enzyme Activation , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/metabolism , Gene Expression Regulation, Enzymologic , Glioma/pathology , Glioma/enzymology , Metalloendopeptidases/genetics , Papio , Tissue Inhibitor of Metalloproteinase-2/genetics , Tissue Inhibitor of Metalloproteinase-1/genetics , Tumor Cells, CulturedABSTRACT
To evaluate possible roles of matrix metalloproteinase (MMP)-1, -2, tissue inhibitor of metalloproteinase (TIMP)-1, -2 and membrane-type-1 matrix metalloproteinase (MT1-MMP) in invasion of human gliomas, expressions of these proteins were investigated in ten cases of human glioma and two meningioma tissues and eight human glioma cell lines. In gelatin zymography, MMP-2 activities of glioblastomas were higher than astrocytomas. The activated form of MMP-2 was seen in five of six cases of glioblastomas, but not in astrocytomas. MMP-9 activity was detected in all cases of malignant astrocytomas but the reactivity of MMP-9 was weaker than that of MMP-2. MT1-MMP mRNA expression in glioblastomas was higher than that in astrocytomas. Five cases of glioblastomas with activated form of MMP-2 had MT1-MMP expressions. In vitro, human glioma cell lines with high expression of MT1-MMP also showed high MMP-2 activity. TIMP-1 transcripts were constitutively present in almost all glioma tissues and cell lines, whereas TIMP-2 mRNA were weak especially in malignant gliomas. Imbalance of TIMP-2/MMP-2 was observed using immunoprecipitation analysis in a glioma cell line. High expression of MMP-2 and MT1-MMP is possibly involved in invasiveness of malignant glioma.