Hara A, Saegusa M, Ichinoe M, Okayasu I
Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa, 228-8555 Japan.
J Clin Pathol. 2008 Mar;61(3):287-92. doi: 10.1136/jcp.2007.051961. Epub 2007 Dec 21.
Definitive distinction between low-grade astrocytoma and astrogliosis is a long-standing difficulty due to their similar histopathological characteristics. To clarify differences in biological significance, this study focused on various components of the cell cycle machinery and proliferation as key parameters, comparing expression in astrogliosis, as well as low- and high-grade astrocytomas.
The expression of p16, p21 and p27, and cyclin A, cyclin D1, cyclin E, Rb and Ki-67 was immunohistochemically examined in 40 cases of astrogliosis and 48 cases of low-grade astrocytomas (grade II), as well as 50 high-grade tumours (grades III and IV). The results were also compared with survival data for the astrocytomas.
Cell proliferation determined by Ki-67 immunoreactivity did not differ between astrogliosis and low-grade tumours. Average labelling indices (LIs) for p16, p21, Rb, cyclin A and cyclin E showed a stepwise increase from astrogliosis, through low- to high-grade astrocytomas, indicating the possibility that over 9%, 6% and 4% of LIs for p16, p21 and cyclin A, respectively, may be useful predictors in the case of the latter, in contrast to significant decrease in p27 LIs. Significantly higher mean LI values for cyclin D1 were also evident in astrogliosis (12.42) as compared with astrocytomas (low grade, 2.26; high grade, 4.60). Positive correlations between LIs for Rb and Ki-67 were observed with astrogliosis and low- but not high-grade tumours. In addition, high cyclin A LI values were independently associated with poor outcome in low-grade tumours.
These findings provide evidence that expression of cell-cycle-related molecules may be a reliable parameter for differential diagnosis of low-grade astrocytomas and astrogliosis. Moreover, detection of cyclin A appears to be useful for predicting behaviour of low-grade astrocytomas.
由于低级别星形细胞瘤和星形胶质细胞增生症具有相似的组织病理学特征，因此明确区分二者一直是个难题。为阐明生物学意义上的差异，本研究聚焦于细胞周期机制和增殖的各个组成部分作为关键参数，比较了星形胶质细胞增生症以及低级别和高级别星形细胞瘤中的表达情况。
采用免疫组织化学方法检测了40例星形胶质细胞增生症、48例低级别星形细胞瘤（二级）以及50例高级别肿瘤（三级和四级）中p16、p21和p27，以及细胞周期蛋白A、细胞周期蛋白D1、细胞周期蛋白E、视网膜母细胞瘤蛋白（Rb）和Ki-67的表达情况。还将结果与星形细胞瘤的生存数据进行了比较。
通过Ki-67免疫反应性确定的细胞增殖在星形胶质细胞增生症和低级别肿瘤之间没有差异。p16、p21、Rb、细胞周期蛋白A和细胞周期蛋白E的平均标记指数（LIs）从星形胶质细胞增生症到低级别再到高级别星形细胞瘤呈逐步上升趋势，这表明与p27标记指数显著下降相反，p16、p21和细胞周期蛋白A的标记指数分别超过9%、6%和4%时，可能对后者是有用的预测指标。与星形细胞瘤（低级别，2.26；高级别, 4.60）相比，星形胶质细胞增生症中细胞周期蛋白D1的平均标记指数值也明显更高（12.42）。在星形胶质细胞增生症以及低级别而非高级别肿瘤中，观察到Rb和Ki-67的标记指数之间存在正相关。此外，在低级别肿瘤中，高细胞周期蛋白A标记指数值与不良预后独立相关。
这些发现提供了证据，表明细胞周期相关分子的表达可能是低级别星形细胞瘤和星形胶质细胞增生症鉴别诊断的可靠参数。此外，检测细胞周期蛋白A似乎对预测低级别星形细胞瘤行为有用。
