Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have characterized the epidermal growth factor (EGF) receptor in human meningioma (biopsy) microsomes, cellularly derived microsomes, and intact meningioma cells in culture. Scatchard analysis of competition studies reveals both high and low affinity EGF binding sites in the meningiomas tested [dissociation constant (Kd) = 0.9 nM, maximum number of binding sites (Bmax) = 280 fmol/mg protein; Kd = 5.0 nM, Bmax = 660 fmol/mg protein, respectively]. The binding of 125I-EGF is specific since it is abolished by excess unlabeled EGF but not by excess unlabeled platelet-derived growth factor or insulin. Meningioma cultures preincubated with platelet-derived growth factor (10 ng/ml) at 37 degrees C shifted the 125I-EGF competition curve to the right but did not affect receptor number (100,000 sites/cell) when compared to cultures preincubated at 4 degrees C. Cross-linking studies performed with ethyleneglycol bis(succinimidyl succinate) followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography reveal a major band of specifically bound EGF (Mr approximately 150,000), although the normal (Mr approximately 170,000) and another putative proteolytic form (Mr approximately 125,000) can also be seen. These results indicate that human meningiomas contain a mixed population of EGF binding sites and exhibit properties of previously described EGF receptors.
 ...
PMID:Characterization of the epidermal growth factor receptor in human meningioma. 349 42

In this study we evaluated phospholipase C-gamma 1 (PLC-gamma 1) expression, activity, and association with the epidermal growth factor (EGF) receptor in a series of human meningiomas as well as cultured meningioma cells. Phospholipase C-gamma 1 was detectable by immunoblot and immunohistochemistry in 13 of 13 meningioma specimens. Epidermal growth factor receptors were detected by immunoblot in six of nine meningiomas (67%) and by immunohistochemistry in 13 of 19 meningiomas (68%) but not in normal leptomeningeal cells. In two of three meningiomas EGF receptors and/or a 170-kd phosphotyrosine band precipitated with a PLC-gamma 1 antiserum. Both PLC-gamma 1 and EGF receptors also exhibited the same pattern of immunostaining on meningioma tissue sections. Phospholipase C-gamma 1 catalytic activity, measured in a PIP2 hydrolysis assay, was higher in nine EGF receptor-positive meningiomas than in six EGF receptor-negative meningiomas (P = .05; t test). Finally, treatment of cultured meningioma cells with transforming growth factor-alpha induced a 78% increase in PLC-gamma 1 catalytic activity. Thus, these data are consistent with the possibility that the EGF receptor tyrosine kinase regulates PLC-gamma 1 activity in native meningioma tissue.
 ...
PMID:The epidermal growth factor receptor is associated with phospholipase C-gamma 1 in meningiomas. 811 14

Meningiomas arise from the arachnoidal cells surrounding the brain and are one of the most common tumors of the central nervous system. These tumors are known to be hormonally modulated and may occur in association with breast carcinoma. Overexpression of the erbB-2 oncogene product and mutation of the tumor suppressor p53 gene are considered causal driving forces in the pathogenesis of adenocarcinomas of the breast. To determine whether abnormal expression of these genes also plays a role in the pathogenesis of meningiomas, we analyzed the expression of the erbB-2 and p53 proteins in 17 atypical and 35 typical meningioma tissue specimens by immunohistochemistry. The staining intensity was assigned a relative value of 0 to 5+, where 5+ denoted confluent immunoreactivity, 4+ to 1+ denoted varying degrees of focal positivity, and 0 denoted no evidence of staining. Levels of p53 and erbB-2 immunohistochemical staining were then correlated with tumor histology. For p53 immunoreactivity, typical meningiomas had a median staining score of 1.0, compared to 4.0 for atypical meningiomas (P < 0.0001, Mann-Whitney U test). For erbB-2 immunoreactivity, typical meningiomas had a median staining score of 5.0 compared to 1.0 for atypical meningiomas (P < 0.0001, Mann-Whitney U test). The inverse relationship between levels of erbB-2 and p53 immunoreactivity was found to be statistically significant (P < 0.0001, ANOVA). Expression of the erbB-2 protein was not associated with gene amplification or the presence of activating mutation in the transmembrane region of the protein. These findings may improve our understanding of the molecular events that occur in the neoplastic transformation of meningothelial cells. The patterns of erB-2 and p53 immunoreactivity may prove to be useful markers with which to identify potentially more malignant meningiomas.
 ...
PMID:Immunohistochemical evaluation of erbB-2 and p53 protein expression in benign and atypical human meningiomas. 869 33

An unusual posterior fossa neoplasm in a 26-year-old woman with short history of the cerebellar symptoms is presented. CT and MR images showed the tumor within the cerebellopontine angle, suspected as meningioma. At surgery, the tumor was dura-attached and did not infiltrate the arachnoid. Histologically, the neoplasm was a small blue cell tumor with solid and microcystic pattern, consistent with primitive neuroectodermal tumor (PNET). Immunohistochemically the cells were strongly positive for NCAM and GFAP. Fluorescence in situ hybridization (FISH) was performed with the cosmids G9 and F7 (flanking EWSR1/22q12 region) DNA probes and dual-color spectrum-orange LSI HER-2/neu (17q11.2)/spectrum green CEP17 (17p11.1-q11.1) DNA probe. The presence of isochromosome 17q within neoplastic cells was found. The tumor was classified as a medulloblastoma. We demonstrate the utility of a multidisciplinary approach to nervous system tumor diagnosis. The clinical features together with histological, immunohistochemical, and characteristic molecular alteration allowed classification of the presented case.
 ...
PMID:Primitive neuroectodermal tumor in the cerebellopontine angle with isochromosome 17q presenting as meningioma in a woman 26 years of age. 1267 52

Prediction of outcome in patients with meningiomas remains a significant problem to date. We have evaluated the role of symptoms at presentation and overexpression of her-2/neu overexpression as independent prognostic factors in meningiomas. In a retrospective study on patients with biopsy-proven diagnosis of meningioma, her-2/neu overexpression was evaluated using immunohistochemistry (IHC) performed on paraffin-embedded specimens. An IHC score of > or =2+ was considered positive for overexpression. Two hundred thirty-seven patients thus identified between January 1986 and December 1999 included 149 females and 88 males, with a mean age of 63.44 years. Survival was estimated using the Kaplan-Meier method. Incidence of meningiomas in females (62.8%) was significantly greater than in males. Focal neurodeficits, headache, and seizures (39.66%) were the most common presenting complaints and were not related to tumor behavior/outcome. Syncope at presentation was associated with a decreased survival, but this symptom constituted only 2.53% of the total, so reliable conclusions could not be drawn. Only 6 (2.53%) specimens revealed HER-2/neu overexpression by IHC. HER-2/neu overexpression is not a predictor of tumor behavior and has no role as a prognostic factor in meningiomas. Syncope as the clinical presentation at diagnosis may predict a poor outcome, but needs further investigation.
 ...
PMID:Role of her-2/neu overexpression and clinical features at presentation as predictive factors in meningiomas. 1559 9

Meningiomas account for about 15-30% of all primary intracranial tumors. According to the 2007 WHO classification, meningiomas are divided into three grades (I, II and III). Recurrence is an issue following surgical treatment of meningioma, especially in grades II and III. HER2 (also known as erbB-2) is a 185-kD transmembrane glycoprotein with tyrosine kinase activity. HER2 is expressed in some human malignancies and can be a potential target for therapeutic intervention with selective inhibitors. There are only a few studies on the relationship between meningioma and HER2 expression, and the results are different as well. The aim of this study was to determine this relationship. Seventy-two paraffin blocks of meningioma were selected randomly, and immunohistochemical staining was then performed for each specimen. Thirty-one of the 72 meningiomas were HER2-positive. HER2 expression was observed in 11 (55%) of the 20 grade II/III, and 20 (38.5%) of the 52 grade I meningiomas. Consequently, HER2 expression was detected in 43% of meningiomas. No significant difference was seen between grade I and grade II/III meningiomas, primary and recurrent tumors, and males and females from the point of view of HER2 expression.
 ...
PMID:An immunohistochemical study of HER2 expression in meningioma and its correlation with tumor grade. 2242 Sep 24