Strojnik Tadej, Røsland Gro Vatne, Sakariassen Per Oystein, Kavalar Rajko, Lah Tamara
Department of Neurosurgery, Maribor Teaching Hospital, SI-2000 Maribor, Slovenia.
Surg Neurol. 2007 Aug;68(2):133-43; discussion 143-4. doi: 10.1016/j.surneu.2006.10.050. Epub 2007 May 29.
The IF protein nestin and the RNA-binding protein musashi are expressed by neural progenitor cells during CNS development. Their expression in glial tumors was evaluated by immunohistochemistry, and the histopathological scores correlated with levels of cysteine cathepsins that are known prognostic markers in several tumors.
The levels of nestin, musashi, and cathepsins B and L were assessed by immunohistochemical analysis of biopsies from 87 patients with primary CNS tumors. To confirm the immunohistochemical data, nestin expression was analyzed by real-time PCR in 12 brain tumor biopsies. The exact location of nestin-positive cells was determined by mapping the distribution of nestin in a highly invasive human glioma xenograft model.
Immunostaining revealed nestin to be expressed in 95.8% and musashi in 80% of the patient biopsies. The total IHC score for nestin was significantly higher in high- than in low-grade tumors (P < .0001). No difference was observed for musashi (P = .11). Real-time PCR of nestin expression confirmed the immunohistochemical data. Nestin expression was shown to be a strong prognostic marker for decreased overall survival (P = .0001), whereas musashi expression has no prognostic significance. Moreover, nestin was shown by Cox regression analysis to be a stronger prognostic marker than cathepsins B and L. IHC staining of nestin in a xenograft model showed that its expression is localized mainly in the invasive tumor cells at the tumor periphery.
Nestin is shown to be a strong prognostic marker for glioma malignancy. The presented data links the invasive glioma cells to CNS precursor cells, indicating that the most malignant cells in the gliomas may well be closely related to the glioma stem cells.
中间丝蛋白巢蛋白和RNA结合蛋白马斯ashi在中枢神经系统发育过程中由神经祖细胞表达。通过免疫组织化学评估它们在胶质瘤中的表达，并将组织病理学评分与半胱氨酸组织蛋白酶水平相关联，半胱氨酸组织蛋白酶是几种肿瘤中已知的预后标志物。
通过对87例原发性中枢神经系统肿瘤患者的活检组织进行免疫组织化学分析，评估巢蛋白、马斯ashi以及组织蛋白酶B和L的水平。为了证实免疫组织化学数据，在12例脑肿瘤活检组织中通过实时PCR分析巢蛋白的表达。通过绘制巢蛋白在高度侵袭性人胶质瘤异种移植模型中的分布，确定巢蛋白阳性细胞的确切位置。
免疫染色显示，95.8%的患者活检组织中表达巢蛋白，80%的患者活检组织中表达马斯ashi。巢蛋白的总免疫组化评分在高级别肿瘤中显著高于低级别肿瘤（P <.0001）。马斯ashi未观察到差异（P =.11）。巢蛋白表达的实时PCR证实了免疫组织化学数据。巢蛋白表达被证明是总体生存率降低的强有力预后标志物（P =.0001），而马斯ashi表达无预后意义。此外，通过Cox回归分析显示，巢蛋白是比组织蛋白酶B和L更强的预后标志物。异种移植模型中巢蛋白的免疫组化染色显示，其表达主要定位于肿瘤周边的侵袭性肿瘤细胞中。
巢蛋白被证明是胶质瘤恶性程度的强有力预后标志物。所呈现的数据将侵袭性胶质瘤细胞与中枢神经系统前体细胞联系起来，表明胶质瘤中最恶性的细胞可能与胶质瘤干细胞密切相关。
