title: Expression of oligodendroglial and astrocytic lineage markers in diffuse gliomas: use of YKL-40, ApoE, ASCL1, and NKX2-2.
abstract: The phenotypic heterogeneity of astrocytic and oligodendroglial tumor cells complicates establishing accurate diagnostic criteria, and lineage-specific markers would facilitate diagnosis of glioma subtypes. Based on data from the literature and from expression microarrays, we selected molecules relevant to gliogenesis and glial lineage specificity and then used immunohistochemistry to assess expression of these molecules in 55 diffuse gliomas, including 8 biphasic oligoastrocytomas, 21 oligodendrogliomas (all with 1p/19qloss), 21 astrocytomas, and 5 glioblastomas. For the astrocytic lineage markers (GFAP, YKL-40, and ApoE), GFAP expression was significantly higher in the astrocytic component of oligoastrocytomas compared with the oligodendroglial part; similar patterns were detected for YKL-40 and ApoE, although the differences were not significant. GFAP, YKL-40, and ApoE reliably distinguished grade II-III oligodendrogliomas from grade II-IV astrocytomas (p < 0.0001, p = 0.002, and p < 0.0001, respectively). Among the oligodendroglial lineage markers (Olig2, Sox10, ASCL1, and NKX2-2), ASCL1 and NKX2-2 displayed significantly different immunostaining between oligodendrogliomas and astrocytomas (p = 0.017 and 0.004, respectively), but none clearly differentiated between the 2 glial populations of oligoastrocytomas. In addition to GFAP, therefore, YKL-40, ApoE, ASCL1, and NKX2-2 represent promising tumor cell markers to distinguish oligodendrogliomas from astrocytomas.
authors.affiliation: Molecular Pathology Unit, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA.
authors.forename: Audrey
authors.initials: A
authors.lastname: Rousseau
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Nutt
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Betensky
authors.forename: A John
authors.initials: AJ
authors.lastname: Iafrate
authors.forename: Moonjoo
authors.initials: M
authors.lastname: Han
authors.forename: Keith L
authors.initials: KL
authors.lastname: Ligon
authors.forename: David H
authors.initials: DH
authors.lastname: Rowitch
authors.forename: David N
authors.initials: DN
authors.lastname: Louis
mesh_terms: D054392:Adipokines; D001057:Apolipoproteins E / Q000032:analysis / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D001254:Astrocytoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D019070:Cell Lineage / Q000235:genetics*; D000071451:Chitinase-3-Like Protein 1; D003937:Diagnosis, Differential; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis / Q000378:metabolism; D005910:Glioma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D006023:Glycoproteins / Q000032:analysis / Q000378:metabolism; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D037102:Lectins; D009687:Nuclear Proteins; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology*; D009837:Oligodendroglioma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D011237:Predictive Value of Tests; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism; D029961:Zebrafish Proteins
chemical_list: D054392:Adipokines; D001057:Apolipoproteins E; D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D000071451:Chitinase-3-Like Protein 1; D005904:Glial Fibrillary Acidic Protein; D006023:Glycoproteins; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D037102:Lectins; D009687:Nuclear Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C065500:ASCL1 protein, human; C084533:CHI3L1 protein, human; C000715631:NKX2-2 protein, human; C040661:apolipoprotein E1; C000715630:nkx2.2b protein, zebrafish