Hunter Stephen, Young Andrew, Olson Jeffrey, Brat Daniel J, Bowers Geoffrey, Wilcox Josiah N, Jaye David, Mendrinos Savvas, Neish Andrew
Department of Pathology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
J Neuropathol Exp Neurol. 2002 Mar;61(3):275-81. doi: 10.1093/jnen/61.3.275.
Fibrillary astrocytoma, the most common primary central nervous system neoplasm, is infiltrating, rapidly proliferating, and almost invariably fatal. This contrasts with the biologically distinct pilocytic astrocytoma, which is circumscribed, often cystic, slowly proliferating, and associated with a favorable long-term outcome. Diagnostic markers for distinguishing pilocytic astrocytomas from infiltrating anaplastic astrocytomas are currently not available. To identify genes that might either serve as markers or explain these distinct biologic behaviors, cDNA microarray analysis was used to compare the expression of 7,073 genes (nearly one quarter of the human genome) between these 2 types of astrocytoma. Messenger RNAs pooled from 3 pilocytic astrocytomas and from 4 infiltrating anaplastic astrocytomas were compared. Apolipoprotein D (apoD), which expressed 8.5-fold higher in pilocytic astrocytomas, showed the greatest level of differential expression and emerged as a potential marker for pilocytic tumors. By immunohistochemistry, 10 of 13 pilocytic astrocytomas stained positively for apoD, while none of 21 infiltrating astrocytomas showed similar staining. ApoD immunostaining was also seen in 9 of 14 of gangliogliomas, 4 of 5 subependymal giant cell astrocytomas (SEGAs), and a single pleomorphic xanthoastrocytomas (PXAs). By in situ hybridization, pilocytic astrocytomas, in contrast with infiltrating astrocytomas, showed widespread increased apoD expression. SAGE analysis using the NCBI database showed a higher level of expression of apoD RNA in pilocytic astrocytoma than in any of the other 94 neoplastic and non-neoplastic tissues in the database. ApoD is associated with decreased proliferation in some cell lines, and is the protein found in highest concentration in cyst fluid from benign cystic disease of the breast. ApoD might play a role in either decreased proliferation or cyst formation in pilocytic astrocytomas, gangliogliomas, SEGAs, and PXAs.
纤维性星形细胞瘤是最常见的原发性中枢神经系统肿瘤，具有浸润性、快速增殖性，几乎总是致命的。这与生物学特性截然不同的毛细胞型星形细胞瘤形成对比，毛细胞型星形细胞瘤边界清晰，常为囊性，增殖缓慢，且长期预后良好。目前尚无区分毛细胞型星形细胞瘤与浸润性间变性星形细胞瘤的诊断标志物。为了鉴定可能作为标志物或解释这些不同生物学行为的基因，采用cDNA微阵列分析来比较这两种类型星形细胞瘤之间7073个基因（近人类基因组的四分之一）的表达情况。对从3例毛细胞型星形细胞瘤和4例浸润性间变性星形细胞瘤中提取的信使RNA进行了比较。载脂蛋白D（apoD）在毛细胞型星形细胞瘤中的表达高8.5倍，显示出最大程度的差异表达，并成为毛细胞型肿瘤的潜在标志物。通过免疫组织化学方法，13例毛细胞型星形细胞瘤中有10例apoD染色呈阳性，而21例浸润性星形细胞瘤中无一例显示类似染色。在14例神经节胶质瘤中的9例、5例室管膜下巨细胞星形细胞瘤（SEGA）中的4例以及1例多形性黄色星形细胞瘤（PXA）中也观察到了apoD免疫染色。通过原位杂交，与浸润性星形细胞瘤相比，毛细胞型星形细胞瘤显示出广泛增加的apoD表达。使用NCBI数据库进行的SAGE分析表明，毛细胞型星形细胞瘤中apoD RNA的表达水平高于数据库中其他94种肿瘤性和非肿瘤性组织中的任何一种。ApoD与某些细胞系中的增殖减少有关，并且是乳腺良性囊性疾病囊液中浓度最高的蛋白质。ApoD可能在毛细胞型星形细胞瘤、神经节胶质瘤、SEGA和PXA的增殖减少或囊肿形成中发挥作用。
