title: Polysialic acid is associated with better prognosis and IDH1-mutation in diffusely infiltrating astrocytomas.
abstract: BACKGROUND
  The aim of the study was to assess the localization of Polysialic acid (polySia) and Neural cell adhesion molecule (NCAM) in grade I-IV astrocytomas by confocal microscopy, and also to clarify and compare their relationship to conventional clinicopathological features in these tumors.
  
  
  METHODS
  Study material was stained immunohistochemically for polySia, NCAM and IDH1-R132H point mutation. Confocal microscopy of polySia and NCAM staining was performed on tissue micro-array samples (TMA) of 242 diffusely infiltrating astrocytomas (grade II: 28; grade III: 33; grade IV: 181) and 82 pilocytic astrocytomas. The results were statistically correlated to clinicopathological factors and survival data.
  
  
  RESULTS
  PolySia was observed in 45 cases (19%) and NCAM positivity in 92 cases (38%). All 45 tumors with polySia positivity were also positive for NCAM whereas there were 47 tumors which contained positive staining for NCAM but not for polySia. The simultaneous expression was concomitant and colocalized suggesting polysialyated NCAM (polySia-NCAM). PolySia expression was significantly stronger in IDH1 mutated tumors than in IDH1 non-mutated (p = 0.001, chi-square test). There were no significant differences in polySia-NCAM between primary tumors or recurrences (p = n.s., chi-square test). PolySia positivity was associated with longer patient survival in relation to total tumor material (p = 0.020, log-rank test). Furthermore, when only glioblastomas were assessed, patients with positive polySia had significantly better prognosis (p = 0.006, log-rank test). In multivariate survival analysis, polySia was found to be an independent prognostic factor. PolySia was nearly absent in grade I pilocytic astrocytomas (1 immunopositive tumor of 82).
  
  
  CONCLUSIONS
  Expression of polySia is common in adult grade II-IV astrocytomas, whereas it is nearly absent in pediatric grade I pilocytic astrocytomas. PolySia positivity is associated with longer survival rates in patients with a grade II-IV astrocytomas and also grade IV glioblastomas assessed separately. The results of this study suggest that IDH1 mutation may be associated with polySia expression pathways in malignant gliomas.
authors.affiliation: University of Tampere, School of Medicine, Biokatu 6, 33520 Tampere, Finland. katri.s.makela@uta.fi.
authors.forename: Katri
authors.initials: K
authors.lastname: Mäkelä
authors.forename: Kristiina
authors.initials: K
authors.lastname: Nordfors
authors.forename: Jukka
authors.initials: J
authors.lastname: Finne
authors.forename: Anne
authors.initials: A
authors.lastname: Jokilammi
authors.forename: Timo
authors.initials: T
authors.lastname: Paavonen
authors.forename: Hannu
authors.initials: H
authors.lastname: Haapasalo
authors.forename: Miikka
authors.initials: M
authors.lastname: Korja
authors.forename: Joonas
authors.initials: J
authors.lastname: Haapasalo
mesh_terms: D000293:Adolescent; D000328:Adult; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D017354:Point Mutation; D011379:Prognosis; D012794:Sialic Acids / Q000378:metabolism*; D016019:Survival Analysis; D046888:Tissue Array Analysis
chemical_list: D019006:Neural Cell Adhesion Molecules; D012794:Sialic Acids; C021319:polysialic acid; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human