Compostella Alessia, Tosoni Alicia, Blatt Valeria, Franceschi Enrico, Brandes Alba A
Department of Medical Oncology, Istituto Oncologico Veneto-IRCCS, Padova, Italy.
J Neurooncol. 2007 Feb;81(3):295-303. doi: 10.1007/s11060-006-9232-z. Epub 2006 Sep 26.
Anaplastic astrocytomas (WHO grade III) constitute about 10% of all gliomas. Definitive data on predictive and prognostic factors are lacking for these neoplasms that are considered the most enigmatic entity among the whole spectrum of astrocytic tumors because of their unclear biologic behavior and variable clinical outcome. Currently, only few factors have been identified as useful for prognosis of anaplastic astrocytoma: age and Karnofsky Performance Status. Attempts have been made to identify biological prognostic factors for response to therapy and clinical outcome, as well as potential targets for new therapies. Potential prognostic biomarkers concern tumor suppressor genes on chromosome 9q that are involved in the RB1 pathway; PTEN, the PI3k/Akt/p70s6k cascade, survivin gene, Formylpeptide receptor, minichromosome maintenance protein 3 and genes on chromosome 7. Furthermore, some angiogenic factors (e.g. hypoxia-inducible factor-1alpha, vascular endothelial growth factor and scatter factor/hepatocyte growth factor) and the methylation status of O6-methylguanine-DNA methyltransferase gene (one of the main effectors of DNA repair system) are emerging novel putative determinants of prognosis. Moreover, recent studies on magnetic resonance imaging characteristics give prognostic significance to the presence of necrosis and enhancement. The state of the art pictured here underlie the recent interest on gene expression profile to identify aberrations useful to understand the biologic behavior of astrocytic tumors. Our knowledge in this field is still limited, and remains an issue of great concern.
间变性星形细胞瘤(世界卫生组织III级)约占所有胶质瘤的10%。对于这些肿瘤,缺乏关于预测和预后因素的确切数据,由于其生物学行为不明且临床结局多变,它们被认为是星形细胞瘤全谱系中最神秘的实体。目前,仅有少数因素被确定对间变性星形细胞瘤的预后有用:年龄和卡氏功能状态。人们已尝试确定用于预测治疗反应和临床结局的生物学预后因素,以及新疗法的潜在靶点。潜在的预后生物标志物涉及9号染色体上参与RB1通路的肿瘤抑制基因;PTEN、PI3k/Akt/p70s6k级联、生存素基因、甲酰肽受体、微小染色体维持蛋白3以及7号染色体上的基因。此外,一些血管生成因子(如缺氧诱导因子-1α、血管内皮生长因子和散射因子/肝细胞生长因子)以及O6-甲基鸟嘌呤-DNA甲基转移酶基因(DNA修复系统的主要效应器之一)的甲基化状态正在成为新的预后推定决定因素。此外,最近关于磁共振成像特征的研究表明坏死和强化的存在具有预后意义。此处描绘的最新技术是近期对基因表达谱感兴趣的基础,以识别有助于理解星形细胞瘤生物学行为的异常。我们在这一领域的知识仍然有限,仍然是一个备受关注的问题。