title: Transcriptional factors for epithelial-mesenchymal transition are associated with mesenchymal differentiation in gliosarcoma.
abstract: Gliosarcoma is a rare variant of glioblastoma characterized by a biphasic pattern of glial and mesenchymal differentiation. It is unclear whether mesenchymal differentiation in gliosarcomas is because of extensive genomic instability and/or to a mechanism similar to epithelial-mesenchymal transition (EMT). In the present study, we assessed 40 gliosarcomas for immunoreactivity of Slug, Twist, matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), which are involved in EMT in epithelial tumors. Nuclear Slug expression was observed in >50% of neoplastic cells in mesenchymal tumor areas of 33 (83%) gliosarcomas, but not in glial areas (P < 0.0001). Nuclear Twist expression was observed in >50% of neoplastic cells in mesenchymal tumor areas of 35 (88%) gliosarcomas, but glial tumor areas were largely negative except in four cases (P < 0.0001). Expression of MMP-2 and MMP-9 was also significantly more extensive in mesenchymal than in glial tumor areas. None of 20 ordinary glioblastomas showed Slug or Twist expression in >10% neoplastic cells. Thus, expression of Slug, Twist, MMP-2 and MMP-9 was characteristic of mesenchymal tumor areas of gliosarcomas, suggesting that mechanisms involved in the EMT in epithelial neoplasms may play roles in mesenchymal differentiation in gliosarcomas.
authors.affiliation: International Agency for Research on Cancer, Lyon.
authors.forename: Masaya
authors.initials: M
authors.lastname: Nagaishi
authors.forename: Werner
authors.initials: W
authors.lastname: Paulus
authors.forename: Benjamin
authors.initials: B
authors.lastname: Brokinkel
authors.forename: Anne
authors.initials: A
authors.lastname: Vital
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakazato
authors.forename: Felice
authors.initials: F
authors.lastname: Giangaspero
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ohgaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000150:complications / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018316:Gliosarcoma / Q000150:complications / Q000473:pathology*; D005911:Gliosis / Q000209:etiology; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051879:Twist-Related Protein 1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9