Abdulrauf S I, Edvardsen K, Ho K L, Yang X Y, Rock J P, Rosenblum M L
Department of Neurosurgery, Henry Ford Hospital, Detroit, Michigan 48202, USA.
J Neurosurg. 1998 Mar;88(3):513-20. doi: 10.3171/jns.1998.88.3.0513.
It has long been recognized that some patients with low-grade astrocytoma may survive for many years, whereas in others the disease follows a more malignant course resulting in a short survival time, usually due to malignant transformation into higher-grade tumors.
The aim of this study was to investigate angiogenesis in the initial biopsy specimen of tumor tissue as a biological marker to identify patients with low-grade astrocytoma who are at high risk of malignant tumor transformation or death.
Tumor tissue was studied in 74 consecutively treated adult patients in whom a diagnosis of diffuse supratentorial hemispheric histologically proven fibrillary low-grade astrocytoma was made and who underwent surgery between January 1972 and January 1994. Studies were conducted using monoclonal antibodies to the antigens of the proliferation-associated Ki-67 (MIB-1), factor VIII, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF). The overall 5-year survival rate for the entire patient population was 65%, with a median survival time of 7.5 years. The total mean follow-up period was 6.1 years. All tumors showed a low proliferative potential at the time of the initial operation, as demonstrated by an MIB-1 labeling index of less than 1.5%. Patients with more than seven microvessels in tumor tissue (29 cases) had a shorter survival time (mean 3.8 years) than those with seven or fewer microvessels (mean survival 11.2 years). This difference in survival times was significant by univariate (p = 0.001) and stepwise multivariate analyses (p < 0.001). Tumors with a larger number of microvessels also had a greater chance of undergoing malignant transformation (p = 0.001). Similarly, significant staining for VEGF was correlated with shorter survival times when using univariate (p = 0.003) and multivariate (p = 0.008) analyses and with a greater chance of malignant transformation (p = 0.002). Patients with tumors staining positive for VEGF (39 individuals) had a median survival time of 5.3 years, and those with tumors negative for VEGF (35 patients) had a median survival time of 11.2 years. No association was observed between bFGF, EGF, and survival or malignant transformation. The stepwise multivariate analysis included histological and clinical variables simultaneously.
The authors have shown that microvessel density and VEGF levels are independent prognostic markers of survival in fibrillary low-grade astrocytoma. This finding leads them to propose that fibrillary diffuse low-grade astrocytoma is not a single pathological entity but is composed of a spectrum of tumors with differing propensities to undergo malignant transformation that is at least partly based on their inherent angiogenic potential.
长期以来人们认识到，一些低级别星形细胞瘤患者可能存活多年，而另一些患者的疾病则呈更恶性的病程，导致生存时间短，这通常是由于恶性转化为更高级别肿瘤所致。
本研究的目的是调查肿瘤组织初始活检标本中的血管生成情况，作为一种生物学标志物，以识别具有恶性肿瘤转化或死亡高风险的低级别星形细胞瘤患者。
对74例连续接受治疗的成年患者的肿瘤组织进行了研究，这些患者被诊断为经组织学证实的弥漫性幕上半球纤维性低级别星形细胞瘤，并于1972年1月至1994年1月期间接受了手术。使用针对增殖相关抗原Ki-67（MIB-1）、因子VIII、血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（bFGF）和表皮生长因子（EGF）的单克隆抗体进行研究。整个患者群体的总体5年生存率为65%，中位生存时间为7.5年。总平均随访期为6.1年。所有肿瘤在初次手术时均显示出低增殖潜能，MIB-1标记指数小于1.5%即证明了这一点。肿瘤组织中微血管多于7个的患者（29例）的生存时间（平均3.8年）比微血管为7个或更少的患者（平均生存11.2年）短。通过单因素分析（p = 0.001）和逐步多因素分析（p < 0.001），生存时间的这种差异具有统计学意义。微血管数量较多的肿瘤发生恶性转化的可能性也更大（p = 0.001）。同样，使用单因素分析（p = 0.003）和多因素分析（p = 0.008）时，VEGF的显著染色与较短的生存时间相关，并且与更大的恶性转化可能性相关（p = 0.002）。VEGF染色阳性的肿瘤患者（39例）的中位生存时间为5.3年，而VEGF染色阴性的肿瘤患者（35例）的中位生存时间为11.2年。未观察到bFGF、EGF与生存或恶性转化之间存在关联。逐步多因素分析同时纳入了组织学和临床变量。
作者表明，微血管密度和VEGF水平是纤维性低级别星形细胞瘤生存的独立预后标志物。这一发现使他们提出，纤维性弥漫性低级别星形细胞瘤不是单一的病理实体，而是由一系列具有不同恶性转化倾向的肿瘤组成，这种倾向至少部分基于其固有的血管生成潜能。
