title: Correlation between EGFR amplification and the expression of microRNA-200c in primary glioblastoma multiforme.
abstract: Extensive infiltration of the surrounding healthy brain tissue is a critical feature in glioblastoma. Several miRNAs have been related to gliomagenesis, some of them related with the EGFR pathway. We have evaluated whole-genome miRNA expression profiling associated with different EGFR amplification patterns, studied by fluorescence in situ hybridization in tissue microarrays, of 30 cases of primary glioblastoma multiforme, whose clinicopathological and immunohistochemical features have also been analyzed. MicroRNA-200c showed a very significant difference between tumors having or not EGFR amplification. This microRNA plays an important role in epithelial-mesenchymal transition, but its implication in the behavior of glioblastoma is largely unknown. With respect to EGFR status our cases were categorized into three groups: high level EGFR amplification, low level EGFR amplification, and no EGFR amplification. Our results showed that microRNA-200c and E-cadherin expression are down-regulated, while ZEB1 is up-regulated, when tumors showed a high level of EGFR amplification. Conversely, ZEB1 mRNA expression levels were significantly lower in the group of tumors without EGFR amplification. Tumors with a low level of EGFR amplification showed ZEB1 expression levels comparable to those detected in the group with a high level of amplification. In this study we provide what is to our knowledge the first report of association between microRNA-200c and EGFR amplification in glioblastomas.
authors: Unidad Central de Investigación en Medicina, Universitat de València, Valencia, Spain.
authors: Eva
authors: E
authors: Serna
authors: Departamento de Patología, Universitat de Valencia, Valencia, Spain.
authors: Concha
authors: C
authors: Lopez-Gines
authors: Fundación de Investigación del Hospital Clínico Universitario de Valencia/INCLIVA, Valencia, Spain.
authors: Daniel
authors: D
authors: Monleon
authors: Fundación de Investigación del Hospital Clínico Universitario de Valencia/INCLIVA, Valencia, Spain.
authors: Lisandra
authors: L
authors: Muñoz-Hidalgo
authors: Departamento de Patología, Universitat de Valencia, Valencia, Spain.
authors: Robert C
authors: RC
authors: Callaghan
authors: Departamento de Patología, Universitat de Valencia, Valencia, Spain.
authors: Rosario
authors: R
authors: Gil-Benso
authors: Department of Neuropathology, Institute for Neurological Research, FLENI, Buenos Aires, Argentina.
authors: Horacio
authors: H
authors: Martinetto
authors: Departamento de Patología, Universitat de Valencia, Valencia, Spain.
authors: Aurelia
authors: A
authors: Gregori-Romero
authors: Servicio de Neurocirugía, Hospital Clínico Universitario de Valencia, Valencia, Spain.
authors: Jose
authors: J
authors: Gonzalez-Darder
authors: Departamento de Patología, Universitat de Valencia, Valencia, Spain.
authors: Miguel
authors: M
authors: Cerda-Nicolas
mesh_terms: D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D015398:Signal Transduction; D016019:Survival Analysis; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D055815:Young Adult; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D015820:Cadherins; D018398:Homeodomain Proteins; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; C512478:EGFR protein, human; D066246:ErbB Receptors