epidermal-growth-factor and Oligodendroglioma

We have previously documented that the vast majority of high-grade gliomas over-express binding sites for interleukin 13 (IL13) in situ. We now extend this analysis to evaluate the distribution of the binding of IL13 among other brain tumors. Tumor specimens from patients with low-grade gliomas, oligodendrogliomas, ependymomas, pilocytic astrocytomas, gliosarcomas, medulloblastomas, meningiomas, and metastases to the brain were analyzed and compared to a new series of glioblastoma multiforme (GBM) samples. Serial tumor tissue sections were incubated with 125I-labeled (i) IL13, (ii) antibody against transferrin (Tf) receptor, and (iii) epidermal growth factor (EGF). Most (17/18) GBMs stained specifically for IL13 binding sites while sections from 3/11 low-grade gliomas, 5/5 high-grade gliomas (grade III), 3/5 oligodendrogliomas (all three were anaplastic), and 1/2 gliosarcomas also showed specific binding for IL13. We did not detect IL13 binding sites in medulloblastomas (0/4) and found them only in 2/20 meningiomas. Metastases to the brain (4/12, i.e., lung adenocarcinomas and renal cell carcinoma) showed some binding of 125I-IL13. The presence of receptors for Tf was ubiquitous among all studied tumors while EGF receptor expression was much more variable. Since it appears that primarily the least differentiated forms of gliomas possess IL13 binding sites in abundance, it is plausible that IL 13 receptor expressed in low-grade gliomas might be a prognostically significant marker associated with their progression to high-grade gliomas. Finally, we demonstrate that the glioma-associated IL13 receptor is truly more restrictive in nature also due to its selective representation among brain tumors of glial origin.

Topics: Adenocarcinoma; Biomarkers, Tumor; Brain Neoplasms; Carcinoma; Cell Transformation, Neoplastic; Disease Progression; Ependymoma; Epidermal Growth Factor; ErbB Receptors; Gene Expression Regulation, Neoplastic; Glioma; Gliosarcoma; Humans; Interleukin-13; Interleukin-13 Receptor alpha1 Subunit; Interleukin-4; Medulloblastoma; Meningeal Neoplasms; Meningioma; Neoplasm Proteins; Oligodendroglioma; Receptors, Interleukin; Receptors, Interleukin-13; Receptors, Transferrin; Recombinant Proteins; Substrate Specificity

To explore the relationship between the proliferative activities, oncoprotein expression, cell differentiation and prognosis of gliomas.. Immunohistochemistry and image analysis were used to study the expression of proliferating cell nuclear antigen (PCNA) and several oncoproteins both qualitatively and quantitatively in 124 brain gliomas.. It was found that the intensities of PCNA reaction were significantly related to both the grade and prognosis of gliomas. Overexpression of c-erbB-2 protein was slightly stronger in well than in poorly-differenciated gliomas. Moreover, the reactions in patients who survived over 5 years were stronger than in those under 5 years. EGF (40.0%), EGFR (91.4%) and p21ras (53.3%) expression levels were related to neigher the grading nor prognosis of this tumor. The positive ratios of the three antibodies to p53 protein were higher in grades II-IV than in grade I gliomas. The intensity of p53 reaction was correlated to that of PCNA.. It is suggested that the aberration of c-erbB-2, p21ras, EGF and EGFR might be the early events in the initiation and progression of gliomas, whereas p53 is involved in all stages of these tumors. PCNA could reflect the degree of malignancy to a certain extent.

Topics: Brain Neoplasms; Cell Division; Epidermal Growth Factor; ErbB Receptors; Glioma; Humans; Oligodendroglioma; Oncogene Proteins; Proliferating Cell Nuclear Antigen; Proto-Oncogene Proteins p21(ras); Receptor, ErbB-2; Survival Rate; Tumor Suppressor Protein p53

The expression of epidermal growth factor receptor (EGF-R) was examined in 27 primary human brain tumors (7 glioblastomas, 10 astrocytomas, 5 oligodendrogliomas, 1 schwannoma, 1 ganglioneuroma, 1 medulloblastoma, 1 ependymoma, 1 histiocytic lymphoma), in 6 brain metastases from lung carcinomas and in 20 meningiomas. Peritumoral tissues histologically normal excised surgically along with a large tumor were used as control. All plasma membranes from brain tissues tested showed specific EGF binding. The EGF receptor is expressed at low levels in the control human brain and at very high levels in 60% of the total intracranial tumors studied. When the various histological types of tumors were analyzed, the higher percentage of positive tumors was found with the meningiomas (85%) and the glioblastomas (71%), while the lower percentage of positivity was found with the oligodendrogliomas (40%) and the astrocytomas (30%). A good correlation between binding and total amount of EGF-R protein detected by Western Blot was also observed.

Topics: Adult; Aged; Astrocytoma; Blotting, Western; Brain Neoplasms; Cell Membrane; Epidermal Growth Factor; ErbB Receptors; Female; Glioma; Humans; Iodine Radioisotopes; Male; Meningioma; Middle Aged; Neurilemmoma; Oligodendroglioma; Radioligand Assay

A variety of tumors with different histologic types are included in a group of brain tumors. Although each histologic type of tumor has its own range of malignancy, the prognosis seems to be affected by several clinical, histologic and cell-biological factors. For example, relative survival rate of patients with glioblastoma is lower if the patient is older than 50 or 60 years. The leptomeningeal dissemination of glioma cells is a sign of poor prognosis. The presence of necrotic foci in the astrocytic tumors suggests shorter astrocytic tumors suggests shorter survival. Using a monoclonal antibody to bromodeoxyuridine (BrdU), the growth activity of the tumor can be estimated by BrdU labeling index (BrdU-LI, %). Higher BrdU-LI is correlated with more malignant histologic features in astrocytic tumors. In meningiomas, higher BrdU-LI is correlated with a more frequent or rapid recurrence of the tumor. The significance of growth factor receptors and oncogene of growth factor receptors and oncogene products as a cell-biologic marker of malignancy was investigated with an immunohistochemical method. Transferrin receptor was demonstrated in all tumors, and epidermal growth factor in about 40% of astrocytic tumors. The immunoreaction to c-myc oncogene product was detected in most astrocytic tumors; with higher intensity in anaplastic astrocytomas and glioblastomas than in low-grade astrocytomas. The role of these markers in the prognosis of brain tumors is, however, still unclear. Total or subtotal resection of glioblastoma results in longer resection of glioblastoma results in longer survival. Both postoperative radiotherapy and chemotherapy are effective. However, maintenance of chemotherapy longer than longer than 2 years does not significantly improve the prognosis.

Topics: Age Factors; Antibodies, Monoclonal; Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; Bromodeoxyuridine; Cell Cycle; Epidermal Growth Factor; ErbB Receptors; Glioblastoma; Humans; Meningioma; Oligodendroglioma; Oncogenes; Prognosis