Zeppernick Felix, Ahmadi Rezvan, Campos Benito, Dictus Christine, Helmke Burkhard M, Becker Natalia, Lichter Peter, Unterberg Andreas, Radlwimmer Bernhard, Herold-Mende Christel C
Division of Neurosurgical Research, Department of Neurosurgery, University of Heidelberg, Germany.
Clin Cancer Res. 2008 Jan 1;14(1):123-9. doi: 10.1158/1078-0432.CCR-07-0932.
The CD133 antigen has been identified as a putative stem cell marker in normal and malignant brain tissues. In gliomas, it is used to enrich a subpopulation of highly tumorigenic cancer cells. According to the cancer stem cell hypothesis, CD133-positive cells determine long-term tumor growth and, therefore, are suspected to influence clinical outcome. To date, a correlation between CD133 expression in primary tumor tissues and patients' prognosis has not been reported.
To address this question, we analyzed the expression of the CD133 stem cell antigen in a series of 95 gliomas of various grade and histology by immunohistochemistry on cryostat sections. Staining data were correlated with patient outcome.
By multivariate survival analysis, we found that both the proportion of CD133-positive cells and their topological organization in clusters were significant (P < 0.001) prognostic factors for adverse progression-free survival and overall survival independent of tumor grade, extent of resection, or patient age. Furthermore, proportion of CD133-positive cells was an independent risk factor for tumor regrowth and time to malignant progression in WHO grade 2 and 3 tumors.
These findings constitute the first conclusive evidence that CD133 stem cell antigen expression correlates with patient survival in gliomas, lending support to the current cancer stem cell hypothesis.
CD133抗原已被确定为正常和恶性脑组织中一种假定的干细胞标志物。在胶质瘤中，它被用于富集具有高度致瘤性的癌细胞亚群。根据癌症干细胞假说，CD133阳性细胞决定肿瘤的长期生长，因此被怀疑会影响临床结果。迄今为止，原发性肿瘤组织中CD133表达与患者预后之间的相关性尚未见报道。
为解决这一问题，我们通过对冷冻切片进行免疫组织化学分析了95例不同分级和组织学类型的胶质瘤中CD133干细胞抗原的表达。染色数据与患者预后相关。
通过多因素生存分析，我们发现CD133阳性细胞的比例及其在簇中的拓扑组织是无进展生存期和总生存期不良的显著（P<0.001）预后因素，与肿瘤分级、切除范围或患者年龄无关。此外，在世界卫生组织2级和3级肿瘤中，CD133阳性细胞的比例是肿瘤复发和恶性进展时间的独立危险因素。
这些发现构成了首个确凿证据，表明CD133干细胞抗原表达与胶质瘤患者的生存相关，为当前的癌症干细胞假说提供了支持。
