title: Stem cell protein BMI-1 is an independent marker for poor prognosis in oligodendroglial tumours.
abstract: OBJECTIVE
  The polycomb factor BMI-1 has recently been implicated in tumorigenesis of the central nervous system in several experimental animal models. However, the significance of BMI-1 in human glioma has not been investigated. Here we describe expression of the polycomb protein BMI-1 and its downstream targets p16(Ink4a) and MDM2 in both high- and low-grade human glioma.
  
  
  METHODS
  Tumour samples were collected from 305 adult patients treated for primary grades 2-4 gliomas between 1980 and 2006 in Finland and Germany. BMI-1, p16 and MDM2 expression was evaluated using immunohistochemistry in representative paraffin-embedded tumour tissue. The significance of observed immunoreactivity, age at onset, gender, histopathological findings and proliferative index was analysed in univariate and multivariate survival models.
  
  
  RESULTS
  BMI-1 was expressed in all histologic types of diffuse gliomas. We found a significant correlation (P = 0.007) between the frequency of BMI-1 immunoreactive tumour cells and poor survival in World Health Organization grades II-III oligodendrogliomas and oligoastrocytomas (n = 62). The median survival of patients grouped by low, intermediate or high frequency of BMI-1 immunoreactive tumour cells was 191 months, 151 months and 68 months, respectively. This association was also significant in the Cox multivariate regression model. Nuclear p16 immunopositivity predicted better survival in astrocytomas and an inverse correlation between p16 expression and the Ki-67 mitotic index was also observed.
  
  
  CONCLUSIONS
  BMI-1 is found in all histological types of gliomas and the relative protein expression of BMI-1 is a novel independent prognostic marker in oligodendroglial tumours.
authors.affiliation: Institute of Biomedicine, University of Helsinki, Helsinki, Finland. valtteri.hayry@helsinki.fi
authors.forename: V
authors.initials: V
authors.lastname: Häyry
authors.forename: O
authors.initials: O
authors.lastname: Tynninen
authors.forename: H K
authors.initials: HK
authors.lastname: Haapasalo
authors.forename: J
authors.initials: J
authors.lastname: Wölfer
authors.forename: W
authors.initials: W
authors.lastname: Paulus
authors.forename: M
authors.initials: M
authors.lastname: Hasselblatt
authors.forename: H
authors.initials: H
authors.lastname: Sariola
authors.forename: A
authors.initials: A
authors.lastname: Paetau
authors.forename: S
authors.initials: S
authors.lastname: Sarna
authors.forename: M
authors.initials: M
authors.lastname: Niemelä
authors.forename: K
authors.initials: K
authors.lastname: Wartiovaara
authors.forename: N N
authors.initials: NN
authors.lastname: Nupponen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression; D005910:Glioma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis*; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000096:biosynthesis; D012097:Repressor Proteins / Q000096:biosynthesis*
chemical_list: C069077:BMI1 protein, human; D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C497206:MDM2 protein, human; D063150:Polycomb Repressive Complex 1; D051736:Proto-Oncogene Proteins c-mdm2