title: Prognostic value of WT1 protein expression level and MIB-1 staining index as predictor of response to WT1 immunotherapy in glioblastoma patients.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Chiba
authors.forename: Naoya
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tsuboi
authors.forename: Carter
authors.initials: C
authors.lastname: Rabo
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Oka
authors.forename: Manabu
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Naoki
authors.initials: N
authors.lastname: Kagawa
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oji
authors.forename: Haruo
authors.initials: H
authors.lastname: Sugiyama
authors.forename: Toshiki
authors.initials: T
authors.lastname: Yoshimine
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000628:therapy*; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis* / Q000628:therapy*; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013194:Staining and Labeling; D025721:WT1 Proteins / Q000008:administration & dosage* / Q000032:analysis*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D025721:WT1 Proteins