Häyry V, Tynninen O, Haapasalo H K, Wölfer J, Paulus W, Hasselblatt M, Sariola H, Paetau A, Sarna S, Niemelä M, Wartiovaara K, Nupponen N N
Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
Neuropathol Appl Neurobiol. 2008 Oct;34(5):555-63. doi: 10.1111/j.1365-2990.2008.00949.x. Epub 2008 Mar 10.
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.
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.
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.
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.
在多个实验动物模型中，多梳蛋白BMI-1最近被认为与中枢神经系统肿瘤发生有关。然而，BMI-1在人类胶质瘤中的意义尚未得到研究。在此，我们描述多梳蛋白BMI-1及其下游靶点p16(Ink4a)和MDM2在高级别和低级别人类胶质瘤中的表达情况。
从1980年至2006年期间在芬兰和德国接受原发性2-4级胶质瘤治疗的305例成年患者中收集肿瘤样本。使用免疫组织化学方法在代表性的石蜡包埋肿瘤组织中评估BMI-1、p16和MDM2的表达。在单变量和多变量生存模型中分析观察到的免疫反应性、发病年龄、性别、组织病理学结果和增殖指数的意义。
BMI-1在所有组织学类型的弥漫性胶质瘤中均有表达。我们发现，在世界卫生组织II-III级少突胶质细胞瘤和少突星形细胞瘤（n = 62）中，BMI-1免疫反应性肿瘤细胞的频率与不良生存之间存在显著相关性（P = 0.007）。根据BMI-1免疫反应性肿瘤细胞的低、中、高频率分组的患者，其中位生存期分别为191个月、151个月和68个月。这种关联在Cox多变量回归模型中也具有显著性。核p16免疫阳性预测星形细胞瘤患者的生存期更好，并且还观察到p16表达与Ki-67有丝分裂指数之间呈负相关。
在所有组织学类型的胶质瘤中均发现BMI-1，并且BMI-1的相对蛋白表达是少突胶质细胞瘤中的一种新型独立预后标志物。
