EGFR Soluble Isoforms and Their Transcripts Are Expressed in Meningiomas
Open Access
- 18 May 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (5), e37204
- https://doi.org/10.1371/journal.pone.0037204
Abstract
The EGFR (epidermal growth factor receptor) is involved in the oncogenesis of many tumors. In addition to the full-length EGFR (isoform a), normal and tumor cells produce soluble EGFR isoforms (sEGFR) that lack the intracellular domain. sEGFR isoforms b, c and d are encoded by EGFR variants 2 (v2), 3 (v3) and 4 (v4) mRNA resulting from gene alternative splicing. Accordingly, the results of EGFR protein expression analysis depend on the domain targeted by the antibodies. In meningiomas, EGFR expression investigations mainly focused on EGFR isoform a. sEGFR and EGFRvIII mutant, that encodes a constitutively active truncated receptor, have not been studied. In a 69 meningiomas series, protein expression was analyzed by immunohistochemistry using extracellular domain targeted antibody (ECD-Ab) and intracellular domain targeted antibody (ICD-Ab). EGFRv1 to v4 and EGFRvIII mRNAs were quantified by RT-PCR and EGFR amplification revealed by MLPA. Results were analyzed with respect to clinical data, tumor resection (Simpson grade), histological type, tumor grade, and patient outcome.Immunochemical staining was stronger with ECD-Ab than with ICD-Ab. Meningiomas expressed EGFRv1 to -v4 mRNAs but not EGFRvIII mutant. Intermediate or high ECD-Ab staining and high EGFRv1 to v4 mRNA levels were associated to a better progression free survival (PFS). PFS was also improved in women, when tumor resection was evaluated as Simpson 1 or 2, in grade I vs. grade II and III meningiomas and when Ki67 labeling index was lower than 10%.Our results suggest that, EGFR protein isoforms without ICD and their corresponding mRNA variants are expressed in meningiomas in addition to the whole isoform a. EGFRvIII was not expressed. High expression levels seem to be related to a better prognosis. These results indicate that the oncogenetic mechanisms involving the EGFR pathway in meningiomas could be different from other tumor types.This publication has 79 references indexed in Scilit:
- CXCR4 suppression attenuates EGFRvIII-mediated invasion and induces p38 MAPK-dependent protein trafficking and degradation of EGFRvIII in breast cancer cellsCancer Letters, 2011
- Molecular determinants of anti-EGFR sensitivity and resistance in metastatic colorectal cancerBritish Journal of Cancer, 2010
- The role of sphingosine kinase-1 in EGFRvIII-regulated growth and survival of glioblastoma cellsJournal of Neuro-Oncology, 2010
- Tumor heterogeneity is an active process maintained by a mutant EGFR-induced cytokine circuit in glioblastomaGenes & Development, 2010
- EGFR isoforms and gene regulation in human endometrial cancer cellsMolecular Cancer, 2010
- Assessment of Epidermal Growth Factor Receptor (EGFR) expression in human meningiomaRadiation Oncology, 2010
- Mutant EGFR is required for maintenance of glioma growth in vivo, and its ablation leads to escape from receptor dependenceProceedings of the National Academy of Sciences of the United States of America, 2010
- Epidermal growth factor receptor serum (sEGFR) level may predict response in patients with EGFR positive advanced colorectal cancer treated with gefitinib?Cancer Chemotherapy and Pharmacology, 2008
- The 2007 WHO Classification of Tumours of the Central Nervous SystemActa Neuropathologica, 2007
- A new mathematical model for relative quantification in real-time RT-PCRNucleic Acids Research, 2001