Prognostic value of WT1 protein expression level and MIB-1 staining index as predictor of response to WT1 immunotherapy in glioblastoma patients
Prognostic value of WT1 protein expression level and MIB-1 staining index as predictor of response to WT1 immunotherapy in glioblastoma patients
复制标题
DOI：
10.1007/s10014-010-0265-9
复制
发表时间：
2010-04-01
影响因子：
3.3
通讯作者：
Yoshimine, Toshiki
中科院分区：
文献类型：
--
作者：
Chiba, Yasuyoshi;Hashimoto, Naoya;Yoshimine, Toshiki
Wilms' tumor 1（WT 1）免疫治疗被认为是治疗恶性胶质瘤的一种创新方法。由于其新奇，仍然缺乏能够准确预测对这种疗法的反应的工具。在这篇文章中，我们研究了WT 1蛋白表达水平（评分1-4）和MIB-1染色指数在预测复发或进展性多形性胶质母细胞瘤患者治疗后生存结局中的作用。对来自37名参加WT 1免疫治疗II期临床试验的患者的肿瘤样本进行了WT 1水平和MIB-1指数的化学分析。结果显示，WT 1高表达组的中位无进展生存期（PFS）较长与低表达组相比，（评分1和2）（20.0周vs. 8.0周; P = 0.022），并且前者的中位总生存期（OS）也长于后者（54.4周vs 28.4周; P = 0.035）。此外，在WT 1高表达组中，中等染色强度（WT 1评分3）的肿瘤具有最长的中位PFS和OS，分别为24.4周和69.4周。另一方面，MIB-1染色指数和生存率之间没有显著相关性。总之，我们的研究表明，WT 1蛋白表达水平，而不是MIB-1染色指数，可用作预测免疫治疗后结果的预后标志物，并且具有中等WT 1表达的肿瘤患者具有最佳的生存结局。
The use of Wilms' tumor 1 (WT1) immunotherapy is considered to be an innovative approach for the treatment of malignant gliomas. Because of its novelty, tools that can accurately predict response to this therapy are still lacking. In this article, we investigated the role of WT1 protein expression level (score 1-4) and MIB-1 staining index in predicting survival outcome after therapy in patients with recurrent or progressive glioblastoma multiforme. Tumor samples from 37 patients enrolled in a phase II clinical trial on WT1 immunotherapy were immunohistochemically analyzed for WT1 levels and MIB-1 index. Results showed that median progression-free survival (PFS) was longer in the WT1 high expression group (score 3 and 4) compared with that of the low expression group (score 1 and 2) (20.0 weeks vs. 8.0 weeks; P = 0.022), and that the median overall survival (OS) was likewise longer in the former compared to the latter group (54.4 weeks vs. 28.4 weeks; P = 0.035). Furthermore, within the WT1 high expression group, tumors with intermediate staining intensity (WT1 score 3) have both the longest median PFS and OS, 24.4 weeks and 69.4 weeks, respectively. On the other hand, no significant correlation was noted between MIB-1 staining index and survival. In conclusion, our study has shown that WT1 protein expression level, not MIB-1 staining index, can be used as a prognostic marker to foretell outcome after immunotherapy, and that patients whose tumors have intermediate WT1 expression have the best survival outcome.