Ohgaki Hiroko, Kleihues Paul
Pathology Group, International Agency for Research on Cancer (HO), F-69372, Lyon, France.
J Neuropathol Exp Neurol. 2005 Jun;64(6):479-89. doi: 10.1093/jnen/64.6.479.
Published data on prognostic and predictive factors in patients with gliomas are largely based on clinical trials and hospital-based studies. This review summarizes data on incidence rates, survival, and genetic alterations from population-based studies of astrocytic and oligodendrogliomas that were carried out in the Canton of Zurich, Switzerland (approximately 1.16 million inhabitants). A total of 987 cases were diagnosed between 1980 and 1994 and patients were followed up at least until 1999. While survival rates for pilocytic astrocytomas were excellent (96% at 10 years), the prognosis of diffusely infiltrating gliomas was poorer, with median survival times (MST) of 5.6 years for low-grade astrocytoma WHO grade II, 1.6 years for anaplastic astrocytoma grade III, and 0.4 years for glioblastoma. For oligodendrogliomas the MSTwas 11.6 years for grade II and 3.5 years for grade III. TP53 mutations were most frequent in gemistocytic astrocytomas (88%), followed by fibrillary astrocytomas (53%) and oligoastrocytomas (44%), but infrequent (13%) in oligodendrogliomas. LOH 1p/19q typically occurred in tumors without TP53 mutations and were most frequent in oligodendrogliomas (69%), followed by oligoastrocytomas (45%), but were rare in fibrillary astrocytomas (7%) and absent in gemistocytic astrocytomas. Glioblastomas were most frequent (3.55 cases per 100,000 persons per year) adjusted to the European Standard Population, amounting to 69% of total incident cases. Observed survival rates were 42.4% at 6 months, 17.7% at one year, and 3.3% at 2 years. For all age groups, survival was inversely correlated with age, ranging from an MST of 8.8 months (<50 years) to 1.6 months (>80 years). In glioblastomas, LOH 10q was the most frequent genetic alteration (69%), followed by EGFR amplification (34%), TP53 mutations (31%), p16INK4a deletion (31%), and PTEN mutations (24%). LOH 10q occurred in association with any of the other genetic alterations, and was the only alteration associated with shorter survival of glioblastoma patients. Primary (de novo) glioblastomas prevailed (95%), while secondary glioblastomas that progressed from low-grade or anaplastic gliomas were rare (5%). Secondary glioblastomas were characterized by frequent LOH 10q (63%) and TP53 mutations (65%). Of the TP53 mutations in secondary glioblastomas, 57% were in hot-spot codons 248 and 273, while in primary glioblastomas, mutations were more evenly distributed. G:C-->A:T mutations at CpG sites were more frequent in secondary than primary glioblastomas, suggesting that the acquisition of TP53 mutations in these glioblastoma subtypes may occur through different mechanisms.
已发表的关于胶质瘤患者预后和预测因素的数据主要基于临床试验和基于医院的研究。本综述总结了瑞士苏黎世州（约116万居民）进行的星形细胞瘤和少突胶质细胞瘤人群研究中的发病率、生存率和基因改变的数据。1980年至1994年间共诊断出987例病例，患者至少随访至1999年。虽然毛细胞型星形细胞瘤的生存率极佳（10年时为96%），但弥漫性浸润性胶质瘤的预后较差，世界卫生组织II级低级别星形细胞瘤的中位生存时间（MST）为5.6年，III级间变性星形细胞瘤为1.6年，胶质母细胞瘤为0.4年。少突胶质细胞瘤II级的MST为11.6年，III级为3.5年。TP53突变在肥胖型星形细胞瘤中最常见（88%），其次是纤维型星形细胞瘤（53%）和少突星形细胞瘤（44%），但在少突胶质细胞瘤中不常见（13%）。1p/19q杂合性缺失通常发生在无TP53突变的肿瘤中，在少突胶质细胞瘤中最常见（69%），其次是少突星形细胞瘤（45%），但在纤维型星形细胞瘤中罕见（7%），在肥胖型星形细胞瘤中不存在。按照欧洲标准人口调整后，胶质母细胞瘤最为常见（每年每10万人中有3.55例），占总发病病例的69%。观察到的生存率在6个月时为42.4%，1年时为17.7%，2年时为3.3%。在所有年龄组中，生存率与年龄呈负相关，MST范围从8.8个月（<50岁）到1.6个月（>80岁）。在胶质母细胞瘤中，10q杂合性缺失是最常见的基因改变（69%），其次是表皮生长因子受体（EGFR）扩增（34%）、TP53突变（31%）、p16INK4a缺失（31%）和PTEN突变（24%）。10q杂合性缺失与任何其他基因改变相关，并且是与胶质母细胞瘤患者较短生存期相关的唯一改变。原发性（新发）胶质母细胞瘤占主导（95%），而由低级别或间变性胶质瘤进展而来的继发性胶质母细胞瘤很少见（5%）。继发性胶质母细胞瘤的特征是频繁的10q杂合性缺失（63%）和TP53突变（65%）。在继发性胶质母细胞瘤的TP53突变中，57%位于热点密码子248和273，而在原发性胶质母细胞瘤中，突变分布更为均匀。继发性胶质母细胞瘤中CpG位点的G:C→A:T突变比原发性胶质母细胞瘤更频繁，这表明这些胶质母细胞瘤亚型中TP53突变的获得可能通过不同机制发生。
