AIMS: 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.
AIMS: 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 humanglioma 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 humanglioma. 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: Aaron Cooper; John van Doorninck; Lingyun Ji; Darren Russell; Marc Ladanyi; Hiroyuki Shimada; Mark Krailo; Richard B Womer; Jessie Hao-ru Hsu; Dafydd Thomas; Timothy J Triche; Richard Sposto; Elizabeth R Lawlor Journal: Clin Cancer Res Date: 2010-11-03 Impact factor: 12.531
Authors: Monica Bartucci; Mohamed S Hussein; Eric Huselid; Kathleen Flaherty; Michele Patrizii; Saurabh V Laddha; Cindy Kui; Rachel A Bigos; John A Gilleran; Mervat M S El Ansary; Mona A M Awad; S David Kimball; David J Augeri; Hatem E Sabaawy Journal: Target Oncol Date: 2017-08 Impact factor: 4.493
Authors: Rikke H Dahlrot; Steinbjørn Hansen; Stine S Jensen; Henrik D Schrøder; Jacob Hjelmborg; Bjarne W Kristensen Journal: Int J Clin Exp Pathol Date: 2014-06-15
Authors: V Häyry; L K Mäkinen; T Atula; H Sariola; A Mäkitie; I Leivo; H Keski-Säntti; J Lundin; C Haglund; J Hagström Journal: Br J Cancer Date: 2010-02-09 Impact factor: 7.640